Affinage

AQP2

Aquaporin-2 · UniProt P41181

Length
271 aa
Mass
28.8 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AQP2 is the vasopressin-regulated water channel of renal collecting duct principal cells whose regulated insertion into the apical plasma membrane controls body water balance; conditional deletion in collecting duct principal cells produces severe nephrogenic diabetes insipidus, establishing its non-redundant role in urinary concentration (PMID:16581908). The channel mediates transepithelial osmotic water transport through its mercury-sensitive pore, and its C-terminus confers the capacity for hormone-regulated trafficking that distinguishes it from AQP1 (PMID:9321919, PMID:9435270). Vasopressin acting through the cAMP/PKA pathway phosphorylates AQP2 at Ser256, which is necessary for regulated apical accumulation; abolishing this site by the R254L mutation causes dominant NDI and traps wild-type AQP2 intracellularly, a defect rescued by the S256D phosphomimic (PMID:10644653, PMID:16120822). AQP2 constitutively recycles through Rab11-positive subapical stores and clathrin/dynamin-dependent endosomal pathways independently of phosphorylation, with Ser256 phosphorylation governing the regulated arm by promoting surface retention, reducing endocytosis, and increasing tetramer membrane mobility (PMID:14519593, PMID:16049696, PMID:22403603, PMID:27801846). Apical delivery requires a VAMP2/VAMP3-syntaxin-3-SNAP23 SNARE complex constrained by Munc18b, annexin-2-dependent vesicle fusion, microtubule-based dynein/dynactin transport, and ERM-mediated cortical actin remodeling, where moesin and ezrin act respectively in fusion-site actin depolymerization and in facilitating endocytosis via direct FERM-domain binding to the AQP2 C-terminus (PMID:9486234, PMID:18505797, PMID:16046477, PMID:28754689, PMID:18389276). A counterbalancing phosphatase and degradation network—PP2C dephosphorylating Ser261, PP2B/PP1/PP2A acting on Ser256/Ser261/Ser264, AKAP-scaffolded PKA constraint, AS160 Rab-GAP activity, and ubiquitin-dependent turnover through NDFIP1/2-NEDD4/NEDD4L and CHIP-HSP70-MDM2 plus phosphorylation-gated LIP5 binding—sets AQP2 surface abundance and degradative fate (PMID:11592953, PMID:28931009, PMID:28710278, PMID:29145196, PMID:28381458, PMID:27488997, PMID:21511697, PMID:29650969). AQP2 abundance and trafficking are additionally tuned by non-vasopressin inputs including angiotensin II, integrin-β1/RGD signaling, calcineurin-NFATc/Wnt5a, and CaSR, and transcription is driven by vasopressin-activated CREB/AP1, NFATc, and tankyrase/β-catenin pathways (PMID:16896188, PMID:17166937, PMID:21691091, PMID:27892464, PMID:25520007, PMID:29212817).

Mechanistic history

Synthesis pass · year-by-year structured walk · 41 steps
  1. 1995 High

    Established that vasopressin acts by redistributing a pre-existing pool of AQP2 rather than only by changing channel expression, defining the regulated-trafficking paradigm and its dependence on microtubules.

    Evidence Immunofluorescence and immunogold EM in Brattleboro rats ± vasopressin, with colchicine disruption

    PMID:7539496

    Open questions at the time
    • Molecular motor and vesicle identity not yet defined
    • Did not identify the phosphorylation switch driving redistribution
  2. 1997 Medium

    Defined the channel structural determinant for water permeation and ER exit, showing C181 is essential for both function and trafficking and that AQP2 differs structurally from AQP1.

    Evidence Oocyte expression of C181S/C181A mutants with osmotic permeability and localization

    PMID:9321919

    Open questions at the time
    • No atomic structure of the pore
    • Mechanism of ER retention upon mutation unresolved
  3. 1997 Medium

    Identified how vasopressin signaling reaches the AQP2 gene, showing CRE/CREB and AP1/c-Fos elements jointly drive promoter activation.

    Evidence Human AQP2 promoter reporter assays in LLC-PK1 with CREB and c-Fos analysis

    PMID:9140044

    Open questions at the time
    • Single-lab promoter assay not validated in vivo
    • Relative contribution of each element unquantified
  4. 1998 Medium

    Localized the trafficking machinery to the channel by showing dynein/dynactin co-isolate with AQP2 vesicles, linking microtubule motors to AQP2 movement.

    Evidence Anti-AQP2 vesicle immunoisolation and double immunogold EM in rat kidney

    PMID:9486234

    Open questions at the time
    • Direct motor-cargo binding not demonstrated
    • Directionality of dynein-driven transport not tested functionally
  5. 1998 Medium

    Demonstrated that the AQP2 C-terminus is the trafficking signal that confers regulated water permeability, separating channel activity from hormonal control.

    Evidence AQP1/AQP2 chimera in LLC-PK1 with transepithelial permeability and mercury inhibition

    PMID:9435270

    Open questions at the time
    • Specific C-terminal residues responsible not mapped here
    • Partial responsiveness of chimera unexplained
  6. 2000 High

    Pinpointed Ser256 as the PKA phosphorylation site governing regulated apical targeting, showing vasopressin redistributes phospho-AQP2 to the apical membrane.

    Evidence Phospho-specific antibodies, immunoEM, immunoblotting in rat kidney with DDAVP and V2R antagonist

    PMID:10644653

    Open questions at the time
    • Downstream effectors reading the phospho-state not identified
    • Role of additional sites not addressed
  7. 2000 Medium

    Showed phosphorylation-independent routes can drive AQP2 insertion, revealing that membrane delivery is not strictly dependent on Ser256 phosphorylation.

    Evidence Okadaic acid ± H89 with water permeability and localization in CD8 cells

    PMID:10806109

    Open questions at the time
    • Identity of phosphorylation-independent pathway undefined
    • Physiological relevance versus regulated pathway unclear
  8. 2000 Medium

    Defined a constitutive recycling route through an acidified, clathrin-associated perinuclear compartment, distinguishing baseline cycling from regulated insertion.

    Evidence 20°C block and bafilomycin A1 with marker colocalization in LLC-PK1

    PMID:10662736

    Open questions at the time
    • Functional role of vesicle acidification not directly tested
    • Single-lab colocalization study
  9. 2001 Medium

    Identified the endosomal phosphatase that reverses AQP2 phosphorylation, showing PP2B/calcineurin dephosphorylates AQP2 within an AKAP-PKA-PKCzeta complex.

    Evidence In vitro dephosphorylation of 32P-AQP2 on purified IMCD endosomes with PP2B inhibitors

    PMID:11592953

    Open questions at the time
    • Site specificity of PP2B not resolved here
    • In vivo relevance to recycling not shown
  10. 2003 High

    Separated constitutive from regulated recycling, establishing that Ser256 phosphorylation is required for vasopressin-induced but not baseline membrane insertion.

    Evidence Dominant-negative dynamin K44A, methyl-β-cyclodextrin, biotinylation with WT and S256A in two cell lines

    PMID:14519593

    Open questions at the time
    • Molecular trigger of constitutive insertion unknown
    • Endocytic adaptors for AQP2 not yet identified
  11. 2005 Medium

    Defined the endosomal recycling itinerary, placing AQP2 in a Rab11 store transiting EEA1 endosomes and assigning microtubule and actin contributions to compartment maintenance and transport.

    Evidence Rab11 RNAi plus microtubule/actin disruptors with endosomal markers in MDCK-AQP2 cells

    PMID:16049696

    Open questions at the time
    • Rab effectors linking AQP2 to Rab11 not identified
    • Single-lab study
  12. 2005 High

    Connected the Ser256 phospho-switch to human disease, showing R254L abolishes phosphorylation, causes dominant NDI, and acts dominant-negatively over wild-type AQP2.

    Evidence Oocyte and MDCK co-expression with phosphorylation and surface assays; S256D rescue

    PMID:16120822

    Open questions at the time
    • Mechanism of dominant-negative tetramer retention not structurally defined
  13. 2005 Medium

    Identified moesin/ERM-driven actin remodeling at fusion sites as a required step in AQP2 delivery to the membrane.

    Evidence Cell fractionation, moesin F-actin-binding peptide, F-actin quantification in renal cells

    PMID:16046477

    Open questions at the time
    • Direct moesin-AQP2 binding not shown here
    • Upstream regulators of moesin activation unclear
  14. 2004 Medium

    Refined the phospho-model by showing Ser256 phosphorylation is necessary but not sufficient and that internalization signals (PGE2, dopamine) act independently of Ser256 dephosphorylation.

    Evidence S256D phosphomimetic, H-89, PGE2/dopamine in MDCK-C7 and rat medulla slices

    PMID:15625084

    Open questions at the time
    • Sustained PKA target beyond AQP2 not defined
    • Internalization signaling mechanism unresolved
  15. 2006 High

    Genetically proved AQP2 in the collecting duct is indispensable for water balance, with no compensation from connecting-tubule AQP2.

    Evidence Hoxb7-Cre conditional knockout with urine output/osmolality and histology

    PMID:16581908

    Open questions at the time
    • Does not address graded versus all-or-none requirement
    • Trafficking defects versus loss of channel not distinguished in vivo
  16. 2006 Medium

    Established angiotensin II as a non-vasopressin input promoting AQP2 membrane targeting via AT1R-cAMP-PKC, broadening upstream control.

    Evidence Primary IMCD cells with candesartan, PKC inhibitor, cAMP and phospho-AQP2 readouts

    PMID:16896188

    Open questions at the time
    • Source of AT1R-driven cAMP not defined
    • In vivo physiological weight unquantified
  17. 2006 Medium

    Showed transcriptional control extends beyond CREB, identifying a calcineurin-NFATc calcium-responsive pathway acting on the AQP2 promoter independent of TonEBP/NFAT5.

    Evidence Promoter mutational analysis, ChIP, NFATc translocation, calcineurin inhibitors

    PMID:17166937

    Open questions at the time
    • Physiological calcium trigger in vivo not defined
    • Crosstalk with tonicity signaling partially resolved
  18. 2006 Medium

    Separated AQP2 surface accumulation from V2R fate, showing AQP2 resides in endocytosis-resistant domains while the receptor is independently internalized, and that VP washout releases an endocytic block.

    Evidence Live-cell imaging of tagged AQP2/V2R with FITC-dextran fluid-phase assay

    PMID:16563128

    Open questions at the time
    • Molecular basis of the endocytosis-resistant domain unknown
    • Nature of the released endocytic block undefined
  19. 2006 Medium

    Revealed a PKA-independent, ERK-dependent route for cAMP to upregulate AQP2 expression, broadening signaling beyond canonical PKA.

    Evidence PKA and ERK inhibitors with AQP2/ERK/CREB immunoblotting in IMCD

    PMID:16844078

    Open questions at the time
    • Direct ERK target driving AQP2 transcription not identified
    • Pharmacology-only dissection
  20. 2008 High

    Defined the fusion machinery for regulated exocytosis, identifying the VAMP2/3-syntaxin-3-SNAP23 SNARE set and Munc18b as its negative regulator.

    Evidence Co-IP of AQP2 vesicles, SNARE siRNA knockdowns, apical biotinylation in MCD4 cells

    PMID:18505797

    Open questions at the time
    • Trigger linking phospho-AQP2 to SNARE assembly not defined
    • Munc18b release mechanism unknown
  21. 2008 Medium

    Identified annexin-2 as required for cAMP-induced AQP2 vesicle fusion, providing a lipid-raft-associated fusion factor.

    Evidence In vitro AQP2-vesicle/plasma-membrane fusion assay and peptide inhibition in intact cells

    PMID:18389276

    Open questions at the time
    • Relationship between annexin-2 and the SNARE complex unresolved
    • Single-lab reconstitution
  22. 2008 Medium

    Identified AKAP220 as an AQP2-binding scaffold that recruits PKA to enhance AQP2 phosphorylation, linking compartmentalized signaling to the channel.

    Evidence Yeast two-hybrid, colocalization by immunofluorescence/immunoEM, COS-cell phosphorylation assay

    PMID:19008911

    Open questions at the time
    • Direct binding interface not mapped
    • In vivo requirement not tested
  23. 2011 Medium

    Established AS160 as a negative regulator of AQP2 surface delivery acting via PI3K/Akt-controlled Rab-GAP activity.

    Evidence AS160/Akt1 siRNA, surface biotinylation, LY294002 in M-1 and mpkCCDc14 cells

    PMID:21511697

    Open questions at the time
    • Rab target of AS160 GAP activity on AQP2 vesicles not identified
    • Integration with PKA signaling unclear
  24. 2011 High

    Demonstrated direct ezrin-AQP2 binding via the FERM domain and assigned ezrin a role in facilitating AQP2 endocytosis.

    Evidence Co-IP, pulldown with purified ezrin/FERM domain, shRNA knockdown, anti-AQP2 proteomics

    PMID:28754689

    Open questions at the time
    • How phosphorylation gates ezrin engagement not defined
    • Coordination with clathrin endocytosis unresolved
  25. 2011 Medium

    Identified integrin-β1 as a direct AQP2 partner via an RGD motif, with RGD peptides driving membrane accumulation through distinct cAMP or calcium signals.

    Evidence Co-IP in tissue and MCD4 cells, RGD peptides, FRET cAMP and calcium readouts

    PMID:21691091

    Open questions at the time
    • Physiological ligand of this RGD interaction unknown
    • In vivo relevance untested
  26. 2011 Medium

    Showed AQP2 expression itself is required for vasopressin-induced apical F-actin depolymerization, implicating the channel in cytoskeletal remodeling beyond water transport.

    Evidence AQP2 siRNA and F-actin quantification across multiple MDCK/LLC-PK1 lines

    PMID:23213402

    Open questions at the time
    • Mechanism linking AQP2 to actin dynamics undefined
    • Correlative dependence on expression level
  27. 2012 Medium

    Linked AQP2 to TRPV4-mediated calcium signaling and regulatory volume decrease, indicating assembly of an AQP2-TRPV4 osmosensing complex.

    Evidence Calcium imaging, RVD, ruthenium red in isogenic AQP2+ vs AQP2- RCCD1 cells

    PMID:21938744

    Open questions at the time
    • Direct physical AQP2-TRPV4 binding not shown
    • Physiological role in vivo unclear
  28. 2012 Medium

    Mapped how multiple phosphosites tune surface dwell time, showing Ser256 promotes retention and Ser269 contributes to surface persistence using cold-block trafficking assays.

    Evidence 20°C block/rewarming with S256/S261/S269 mutants and marker colocalization in LLC-PK1

    PMID:22403603

    Open questions at the time
    • Kinases for S269 not identified
    • Site interdependence partially resolved
  29. 2013 Medium

    Showed that aberrantly expressed AQP5 directly binds AQP2 and sequesters it in the ER/Golgi, reducing surface expression.

    Evidence Co-IP, surface biotinylation, colocalization in IMCD3, MLE-15, 293T cells

    PMID:23326416

    Open questions at the time
    • Heterotetramer stoichiometry not defined
    • Pathophysiological context of AQP5 expression unclear
  30. 2014 Medium

    Identified tankyrase/β-catenin as a PKA-independent transcriptional arm for vasopressin-induced AQP2 expression.

    Evidence FRET PKA imaging, XAV939, tankyrase/β-catenin siRNA, nuclear translocation in mpkCCDc14

    PMID:25520007

    Open questions at the time
    • β-catenin target elements on AQP2 promoter not mapped
    • In vivo relevance untested
  31. 2016 Medium

    Resolved phosphatase site specificity, assigning PP1/PP2A to S256/S264 surface control and PP2B to S261/S264, revealing dual phosphatase control of S264.

    Evidence Calyculin A and tacrolimus in rat IMCD with phospho-specific antibodies, biotinylation, IHC

    PMID:27488997

    Open questions at the time
    • Spatial segregation of phosphatase action not defined
    • Functional consequence of S264 dual control unclear
  32. 2016 Medium

    Quantified the biophysical readout of the phospho-switch, showing Ser256 phosphorylation increases AQP2 tetramer membrane diffusion with a stoichiometric threshold for retention.

    Evidence kICS live imaging with defined mixed-phosphorylation tetramers in MDCK cells

    PMID:27801846

    Open questions at the time
    • Molecular basis of diffusion-coupled endocytic retention undefined
    • Single-lab biophysical measurement
  33. 2016 Medium

    Identified Wnt5a-calcineurin as a cAMP/PKA-independent route to increase AQP2 abundance and apical targeting, rescuing urine concentration in an NDI model.

    Evidence Wnt5a, calcineurin inhibition, arachidonic acid in NDI mice with urine osmolality

    PMID:27892464

    Open questions at the time
    • Receptor mediating Wnt5a effect on AQP2 unknown
    • Single-lab study
  34. 2017 High

    Defined the ubiquitin-adaptor logic of AQP2 degradation, showing NDFIP1/2 PY-motif adaptors couple NEDD4/NEDD4L to AQP2 for ubiquitination and turnover.

    Evidence Membrane Y2H, Co-IP, siRNA, PY-deletion mutants in HEK293 and mpkCCD

    PMID:28931009

    Open questions at the time
    • Ubiquitination site on AQP2 not mapped
    • Trigger for adaptor recruitment unknown
  35. 2017 Medium

    Showed phosphorylation allosterically gates AQP2 entry into lysosomal degradation by controlling LIP5 binding affinity.

    Evidence Far-Western, microscale thermophoresis, CD spectroscopy with phosphomimetic and truncation mutants

    PMID:28710278

    Open questions at the time
    • In vivo contribution of LIP5 to AQP2 turnover not tested
    • Structural basis of allosteric control undefined
  36. 2017 Medium

    Defined a CHIP-HSP70-MDM2 axis controlling AQP2 proteasomal degradation and HSP70-coupled S261 phosphorylation via ERK.

    Evidence Co-IP, domain mutants (CHIP-delUbox/delTPR, MDM2-delRING), phospho-mutants in MCD4 cells and kidney slices

    PMID:29145196

    Open questions at the time
    • Relative weight of CHIP versus NEDD4 pathways unresolved
    • Direct CHIP-AQP2 versus HSP70-bridged interaction not fully separated
  37. 2017 Medium

    Identified PP2C as the phosphatase for vasopressin-induced S261 dephosphorylation, showing this site is independent of S256 and dispensable for membrane accumulation.

    Evidence Selective phosphatase inhibitors (sanguinarine etc.), S256A mutant, ERK inhibitor in LLC-PK1 and tissue

    PMID:28381458

    Open questions at the time
    • Functional output of S261 dephosphorylation undefined
    • PP2C isoform not identified
  38. 2018 Medium

    Established AKAPs as constraints on PKA toward AQP2, since disrupting the AKAP-PKA interaction increases AQP2 activity and urine osmolality even under V2R inhibition.

    Evidence AKAP-PKA disruptor compounds in vitro and in vivo with V2R inhibition and urine osmolality

    PMID:29650969

    Open questions at the time
    • Which AKAP mediates the constraint in vivo not pinned down
    • Therapeutic durability untested
  39. 2018 Medium

    Defined a CaSR-driven degradation program reducing AQP2 via p38-MAPK/S261 ubiquitination and miR-137 induction, linking calcium sensing to water handling.

    Evidence Phospho/ubiquitinated AQP2 and miR-137 readouts in pendrin/NCC dKO mice with calcilytic NPS2143

    PMID:29212817

    Open questions at the time
    • Direct miR-137 targeting of AQP2 transcript not validated here
    • Single-model study
  40. 2018 Medium

    Showed urinary AQP2 is predominantly exosomal, ESCRT-associated, and retains mercury-sensitive water channel activity, defining a secretory/biomarker fate.

    Evidence Ultracentrifugation, AQP2 IP, LC-MS/MS, stopped-flow permeability of human urinary vesicles

    PMID:29396622

    Open questions at the time
    • Functional role of exosomal AQP2 in vivo unknown
    • Pathway routing AQP2 to exosomes not defined
  41. 2022 Low

    Reported a non-renal-water role in which MIAC micropeptide binds AQP2 to suppress EREG/EGFR-PI3K/AKT/MAPK signaling and tumor progression in renal cell carcinoma.

    Evidence Co-IP, affinity assays, docking, streptavidin pulldown, in vitro and in vivo tumor experiments

    PMID:36117171

    Open questions at the time
    • Outside canonical water-handling context, mechanism not independently confirmed
    • Binding interface not structurally defined
    • Relevance to physiological AQP2 function unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the Ser256 phospho-switch is mechanistically transduced into SNARE-mediated fusion versus endocytic retention at the apical surface, and which scaffolds/effectors physically couple the phosphorylation state to the trafficking and degradation machinery in vivo.
  • No structural model linking phospho-state to SNARE assembly
  • In vivo requirement of most identified partners untested by genetics
  • Integration of competing kinase/phosphatase/ubiquitin inputs not quantitatively modeled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 3
Localization
GO:0005886 plasma membrane 6 GO:0031410 cytoplasmic vesicle 5 GO:0005768 endosome 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2 GO:0005576 extracellular region 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-382551 Transport of small molecules 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
EZRITGB1NDFIP1NEDD4LSNAP23STX3TRPV4VAMP2
Complex memberships
AKAP-PKA-PP2B endosomal signaling complexAQP2-TRPV4 signaling complexVAMP2/VAMP3-syntaxin-3-SNAP23 SNARE complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 AQP2 redistributes from cytoplasmic vesicles to the apical plasma membrane of collecting duct principal cells following vasopressin treatment, as demonstrated by immunofluorescence and immunogold electron microscopy in Brattleboro rats. Microtubule disruption with colchicine scatters AQP2-bearing vesicles throughout the cytoplasm, blocking apical targeting. Immunofluorescence and immunogold electron microscopy in vasopressin-deficient Brattleboro rats ± exogenous vasopressin; colchicine treatment The Journal of membrane biology High 7539496
2000 PKA-dependent phosphorylation of AQP2 at Ser256 is required for vasopressin-induced apical membrane targeting. Phospho-Ser256 AQP2 is present in both apical plasma membrane and intracellular vesicles; V2 receptor blockade causes near-complete disappearance of apical phospho-AQP2, while DDAVP treatment in Brattleboro rats induces a 10-fold increase in apical phospho-AQP2 labeling without changing overall phospho-AQP2 abundance. Phospho-specific antibodies, immunoelectron microscopy, immunoblotting in rat kidney; DDAVP and V2-receptor antagonist treatments American journal of physiology. Renal physiology High 10644653
1997 Vasopressin activates the AQP2 promoter via the adenylate cyclase-coupled V2 receptor through a dual mechanism: phosphorylation of CREB (binding to CRE element) and induction of c-Fos expression (binding to AP1 element). Both elements together are required for promoter activation. Transfection of human AQP2 promoter fragment in LLC-PK1 cells; reporter assay, CREB phosphorylation and c-Fos expression analysis with V2R activation The American journal of physiology Medium 9140044
2006 AQP2 in the collecting duct (CD) is essential for regulation of body water balance; conditional knockout of AQP2 selectively in CD principal cells causes severe nephrogenic diabetes insipidus (10-fold increased urine output, markedly decreased urine osmolality) without compensation by AQP2 in the connecting tubule. Cre/loxP conditional knockout (Hoxb7-Cre for CD-specific deletion); urine output and osmolality measurement; immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 16581908
2003 AQP2 undergoes constitutive, phosphorylation-independent recycling between intracellular stores and the cell surface. Inhibition of clathrin-mediated endocytosis (by dominant-negative dynamin K44A or methyl-β-cyclodextrin) causes rapid plasma membrane accumulation of both wild-type AQP2 and a phosphorylation-deficient S256A mutant, demonstrating that Ser256 phosphorylation is required for regulated (vasopressin-induced) but not constitutive membrane insertion. Dominant-negative dynamin-2/K44A expression; methyl-β-cyclodextrin treatment; cell-surface biotinylation; FITC-dextran uptake assay in LLC-PK1 and IMCD cells American journal of physiology. Renal physiology High 14519593
2006 Angiotensin II increases AQP2 plasma membrane targeting in IMCD cells via AT1 receptor activation; this effect is mediated through increased cAMP levels and is inhibited by PKC inhibition. ANG II potentiates dDAVP-induced AQP2 phosphorylation and membrane targeting. Primary cultured IMCD cells; immunofluorescence microscopy; cAMP measurement; immunoblotting for phospho-AQP2; AT1 receptor blocker candesartan; PKC inhibitor American journal of physiology. Renal physiology Medium 16896188
2004 S256 phosphorylation is necessary but not sufficient for AQP2 plasma membrane expression; active PKA is required for sustained plasma membrane localization. PGE2 and dopamine induce AQP2 internalization independently of AQP2 dephosphorylation at S256, and dopamine causes AQP2 endocytosis in rat kidney inner medulla slices even in the presence of vasopressin. Transiently transfected MDCK-C7 cells with AQP2-WT, AQP2-S256D mutant; PKA inhibitor H-89; PGE2 and dopamine treatment; confocal microscopy; rat kidney inner medulla slice preparations American journal of physiology. Renal physiology Medium 15625084
2006 AQP2 expression is induced by the calcineurin-NFATc signaling pathway in response to calcium signals, independently of TonEBP/NFAT5. Functional NFAT binding sites exist in the proximal AQP2 promoter. Hypertonicity promotes nuclear translocation of NFATc proteins, and calcineurin activity is required for TonEBP/NFAT5 induction by hypertonicity. Mutational analysis of AQP2 promoter; chromatin immunoprecipitation (ChIP); nuclear translocation assays; calcineurin inhibitors; calcium signaling experiments American journal of physiology. Cell physiology Medium 17166937
2000 AQP2 constitutively recycles through a trans-Golgi-associated compartment even in the absence of vasopressin. A 20°C temperature block and the H+-ATPase inhibitor bafilomycin A1 both trap recycling AQP2 in a perinuclear compartment colocalizing with clathrin (not giantin), implicating vesicle acidification in AQP2 recycling. Temperature block (20°C), bafilomycin A1 treatment, colocalization with Golgi and clathrin markers in transfected LLC-PK1 cells American journal of physiology. Renal physiology Medium 10662736
2000 The serine/threonine phosphatase inhibitor okadaic acid induces AQP2 translocation to the apical membrane independently of AQP2 phosphorylation. When okadaic acid is combined with the PKA inhibitor H89 (eliminating AQP2 phosphorylation), AQP2 still translocates to the apical membrane, indicating that phosphorylation-independent pathways can drive AQP2 insertion. In vivo phosphorylation studies; PKA inhibitor H89; confocal microscopy; osmotic water permeability measurement in AQP2-transfected CD8 cells Journal of cell science Medium 10806109
2005 AQP2 is stored in a Rab11-positive subapical compartment. After vasopressin-induced translocation to the plasma membrane, AQP2 is endocytosed into EEA1-positive early endosomes and then returned to the Rab11-positive subapical compartment. siRNA depletion of Rab11 impairs retention at the subapical storage compartment. Microtubules maintain the distribution of the subapical AQP2 storage compartment, while actin filaments regulate trafficking from early endosomes to the storage compartment. Double immunolabeling with endosomal markers; RNAi knockdown of Rab11; nocodazole/colcemid (microtubule disruption); cytochalasin D/latrunculin B (actin disruption) in MDCK cells expressing AQP2 Histochemistry and cell biology Medium 16049696
2005 The AQP2-R254L mutation (destroying the PKA consensus site around Ser256) causes dominant nephrogenic diabetes insipidus by preventing Ser256 phosphorylation. AQP2-R254L is retained intracellularly, does not traffic to the membrane upon forskolin stimulation, and—when co-expressed with wild-type AQP2—retains wild-type AQP2 in intracellular vesicles. Introducing S256D into AQP2-R254L restores membrane targeting. Oocyte expression; MDCK cell co-expression; immunofluorescence; phosphorylation assays; cell surface expression analysis Journal of the American Society of Nephrology : JASN High 16120822
1998 Cytoplasmic dynein and dynactin colocalize with AQP2-bearing vesicles in renal collecting duct principal cells. Dynein and dynactin are present in membrane fractions enriched for intracellular vesicles and co-immunoisolated with anti-AQP2 antibodies. Quantitative double immunogold labeling confirms colocalization of AQP2 and dynein in the same vesicles. Immunoblotting of membrane fractions; anti-AQP2 immunoisolation of vesicles; quantitative double immunogold EM in rat kidney The American journal of physiology Medium 9486234
2001 AQP2 is a substrate for the protein phosphatase PP2B (calcineurin) within an AKAP-signaling complex on IMCD heavy endosomes. Endosomal PP2B dephosphorylates 32P-labeled AQP2 in vitro; this is inhibited by the PP2B inhibitors EDTA and cyclosporin A-cyclophilin complex. The AKAP complex on endosomes also contains type II PKA regulatory subunit (RII) and PKCzeta. Purification of IMCD heavy endosomes; cAMP-agarose affinity chromatography; small-particle flow cytometry; in vitro dephosphorylation assay with 32P-AQP2; PP2B inhibitors American journal of physiology. Renal physiology Medium 11592953
2008 AQP2 exocytosis to the apical membrane of renal collecting duct cells requires VAMP2, VAMP3 (on AQP2 vesicles), and syntaxin-3 (Stx3) and SNAP23 (on apical plasma membrane) as the functional SNARE complex. Munc18b acts as a negative regulator of SNARE complex formation; Munc18b knockdown causes a 7-fold increase in apical AQP2 without forskolin stimulation. Co-immunoprecipitation confirms Stx3 complexes with VAMP2, VAMP3, SNAP23, and Munc18b. Co-immunoprecipitation of immunoisolated AQP2 vesicles; siRNA knockdown of individual SNAREs; apical surface biotinylation in MCD4 renal cells Journal of cell science High 18505797
2008 AKAP220 directly binds AQP2 (identified by yeast two-hybrid screen) and colocalizes with AQP2 in the cytosol of inner medullary collecting duct cells by double immunofluorescence and immunoelectron microscopy. AKAP220 co-expression increases forskolin-mediated AQP2 phosphorylation in COS cells, suggesting it recruits PKA to phosphorylate AQP2. Yeast two-hybrid screen; double immunofluorescence and immunoelectron microscopy; COS cell co-expression with forskolin stimulation Kidney international Medium 19008911
2005 ERM (ezrin/radixin/moesin) proteins, specifically moesin, are required for actin remodeling during AQP2 vesicular trafficking to the plasma membrane. Forskolin stimulation causes redistribution of moesin to the cell cortex and its enrichment in the particulate fraction. A moesin F-actin binding domain peptide mimics forskolin effects (decreases F-actin, translocates moesin, induces AQP2 translocation) and reduces phosphorylated (active) moesin, pointing to a dual role for moesin in actin depolymerization and cytoskeletal reorganization at AQP2 vesicle fusion sites. Cell fractionation; Triton X-100 extraction; introduction of moesin peptide; confocal microscopy; F-actin quantification in renal cells Journal of cell science Medium 16046477
2011 Ezrin directly interacts with AQP2 through its N-terminal FERM domain binding to the AQP2 C-terminus. This was demonstrated by co-IP with anti-AQP2 and anti-ezrin antibodies, and by pulldown with purified full-length and FERM-domain recombinant ezrin. Ezrin knockdown (shRNA) results in increased membrane AQP2 accumulation and reduced AQP2 endocytosis, establishing that ezrin facilitates AQP2 endocytosis. Co-immunoprecipitation; pulldown with purified recombinant proteins; shRNA knockdown; immunofluorescence; proteomic analysis of anti-AQP2 co-IP complex Journal of cell science High 28754689
2011 AQP2 expression is required for vasopressin/forskolin-mediated F-actin depolymerization at the apical membrane of renal epithelial cells. The degree of F-actin depolymerization correlates with AQP2 expression levels; siRNA knockdown of AQP2 significantly reduces this response. The effect is independent of the polarity of AQP2 membrane insertion. F-actin quantification; immunofluorescence; siRNA knockdown of AQP2; multiple MDCK and LLC-PK1 cell lines with varying AQP2 levels Biology open Medium 23213402
2008 Annexin-2 is required for cAMP-induced AQP2 exocytosis. Forskolin stimulation increases annexin-2 abundance in the plasma membrane fraction and enriches it in lipid rafts. An N-terminal annexin-2 peptide inhibits in vitro fusion of purified AQP2 vesicles with plasma membranes and prevents the forskolin-induced increase in osmotic water permeability in intact cells. Cell fractionation; lipid raft analysis; in vitro vesicle-plasma membrane fusion fluorescence assay with purified AQP2 vesicles; peptide inhibition in intact cells Pflugers Archiv : European journal of physiology Medium 18389276
2017 NEDD4 and NEDD4L E3 ubiquitin ligases mediate ubiquitination and degradation of AQP2, but require adaptor proteins NDFIP1 or NDFIP2 (containing PY motifs that bind NEDD4 family members) to connect them to AQP2. NDFIP1/2 were identified as AQP2-binding partners by Membrane Yeast Two-Hybrid. In HEK293 cells, NDFIP1/2 are essential for NEDD4/NEDD4L-mediated AQP2 ubiquitination and degradation; PY-lacking NDFIP1/2 mutants abolish this effect. In mpkCCD cells, NDFIP1 (not NDFIP2) knockdown increases AQP2 abundance. Membrane Yeast Two-Hybrid; siRNA knockdown; co-immunoprecipitation; ubiquitination assay in HEK293 and mpkCCD cells PloS one High 28931009
2017 Phosphorylation of AQP2 allosterically controls its interaction with the lysosomal trafficking protein LIP5. Non-phosphorylated AQP2 binds LIP5 with the highest affinity. Phospho-mimicking mutations reduce LIP5 binding affinity (most prominently AQP2-S256E), while an AQP2 C-terminal truncation lacking all phosphorylation sites (ΔP242) shows 20-fold lower affinity. This suggests that phosphorylation-dependent LIP5 interaction controls AQP2 targeting to multivesicular bodies/lysosomal degradation. Far-Western blot; microscale thermophoresis (MST); CD spectroscopy; phospho-mimicking mutants (S256E, S261E, S264E, T269E, S256E/T269E) and truncation mutant The Journal of biological chemistry Medium 28710278
2017 AQP2 abundance is regulated by the E3 ligase CHIP via HSP70. CHIP complexes with AQP2 in renal tissue. CHIP expression increases proteasomal degradation of AQP2 and elevates HSP70, which promotes AQP2 phosphorylation at S261 via ERK signaling. HSP70 binding to AQP2 is phosphorylation-dependent (decreased with S256D/S261D mutants). CHIP acts through MDM2 E3 ligase (not directly); co-expression of CHIP with inactive MDM2-delRING impairs AQP2 degradation. Co-immunoprecipitation; immunoblotting; phospho-AQP2 mutants; CHIP-delUbox and CHIP-delTPR domain mutants; MDM2-delRING co-expression in MCD4 cells and kidney slices Cellular physiology and biochemistry Medium 29145196
2017 Protein phosphatase 2C (PP2C) is responsible for vasopressin-induced dephosphorylation of AQP2 at Ser261. The specific PP2C inhibitor sanguinarine abolishes VP-induced S261 dephosphorylation, while PP1 inhibitors, okadaic acid (PP2A), and cyclosporine (PP2B) do not. S261 phosphorylation state is independent of S256 phosphorylation status (shown using AQP2-S256A mutant). Blocking S261 dephosphorylation does not inhibit VP-induced AQP2 membrane accumulation. Pharmacological phosphatase inhibitors (sanguinarine, okadaic acid, cyclosporine, PP1 inhibitors); AQP2-S256A mutant; ERK inhibitor PD98059; LLC-PK1 cells and kidney tissue American journal of physiology. Renal physiology Medium 28381458
2016 PP1/PP2A regulates phosphorylation and apical plasma membrane accumulation of AQP2 at S256 and S264. PP2B regulates S261 and S264 phosphorylation but does not affect total AQP2 plasma membrane abundance. Both PP1/PP2A and PP2B regulate S264 phosphorylation, revealing dual phosphatase control of this site. Calyculin A (PP1/PP2A inhibitor) and tacrolimus (PP2B inhibitor) treatment of rat inner medullary IMCD; immunoblotting, cell surface biotinylation, immunohistochemistry for phospho-AQP2 species American journal of physiology. Renal physiology Medium 27488997
2011 AS160, an Akt substrate containing a Rab-GAP domain, negatively regulates AQP2 trafficking to the plasma membrane. dDAVP stimulates phosphorylation of Akt (S473) and AS160 via PI3K/Akt pathway. siRNA-mediated AS160 knockdown significantly increases plasma membrane AQP2 expression without dDAVP stimulation, as shown by immunocytochemistry and surface biotinylation. siRNA knockdown of AS160 and Akt1; immunocytochemistry; cell surface biotinylation; PI3K inhibitor LY294002; immunoblotting in M-1 and mpkCCDc14 cells American journal of physiology. Renal physiology Medium 21511697
2011 AQP2 directly binds integrin β1 through a conserved RGD domain in its external C-loop. Co-immunoprecipitation demonstrates AQP2-integrin β1 interaction in renal tissue and MCD4 cells. Synthetic RGD-containing peptides (GRGDNP, GRGDSP) increase AQP2 membrane expression independently of hormonal stimulation via distinct intracellular signals (cAMP or calcium, respectively). Co-immunoprecipitation; cell surface biotinylation; confocal microscopy; FRET-based cAMP assay; calcium measurement in MCD4 cells Cellular physiology and biochemistry Medium 21691091
2012 AQP2 functionally interacts with TRPV4 in renal cortical collecting duct cells. Hypotonicity activates TRPV4 and induces Ca2+ influx only in cells expressing AQP2 (not in cells lacking AQP2). TRPV4 blockade with ruthenium red abolishes calcium influx and regulatory volume decrease (RVD). Hypotonicity induces TRPV4 translocation to the plasma membrane only when AQP2 is present, suggesting assembly of AQP2-TRPV4 signaling complex. Calcium fluorescence imaging; RVD measurement; ruthenium red inhibition; TRPV4 expression analysis in AQP2-transfected vs. WT RCCD1 cells Journal of cellular biochemistry Medium 21938744
2016 Wnt5a regulates AQP2 protein expression, phosphorylation, and trafficking through calcineurin signaling, independently of cAMP/PKA pathway. In an NDI mouse model, Wnt5a increases apical membrane AQP2 localization and urine osmolality. Arachidonic acid (a calcineurin activator) mimics vasopressin effects on AQP2. Wnt5a treatment; calcineurin inhibition; arachidonic acid treatment; NDI mouse model; immunofluorescence; urine osmolality measurement Nature communications Medium 27892464
2018 Disruption of AKAP-PKA interaction (using compound FMP-API-1 and derivatives) increases PKA activity and AQP2 channel activity in cortical collecting duct cells. In vivo, this increases AQP2 activity to the same extent as vasopressin and increases urine osmolality even under V2R inhibition, placing AKAPs as regulators that constrain PKA activity toward AQP2 in collecting duct cells. AKAP-PKA disruptor compounds; in vivo mouse experiments with V2R inhibition; cortical collecting duct cell assays; urine osmolality measurement Nature communications Medium 29650969
2006 After vasopressin stimulation, AQP2 accumulates at the cell surface in 'endocytosis-resistant' membrane domains, while the V2 receptor is actively internalized—these are independent events. AQP2 endocytosis and V2R endocytosis are separable temporally and spatially; cAMP elevation per se (by forskolin) does not induce V2R internalization but does cause AQP2 membrane accumulation. After VP washout, AQP2 is progressively internalized together with FITC-dextran (fluid-phase marker), indicating that VP washout releases an endocytic block. Live-cell confocal imaging of epitope-tagged AQP2 and V2R; FITC-dextran fluid-phase endocytosis assay; forskolin vs VP comparison; polarized VP application on filter-grown cells Biology of the cell Medium 16563128
2012 Phosphorylation at S256 promotes AQP2 retention at the plasma membrane while S269 also contributes to surface retention. AQP2-S256D (phosphomimetic) persists on the plasma membrane during 20°C cold block (which traps AQP2 at current location). AQP2-S256A internalizes most rapidly; S269D shows biphasic internalization. After rewarming, WT AQP2, S261A, and S269D recycle rapidly, while S256A dissipates more slowly. 20°C cold block and rewarming in LLC-PK1 cells; phospho-mutants (S256A/D, S261A, S269A/D); colocalization with clathrin, HSP70, EEA1, GM130, Rab11 vesicular markers PloS one Medium 22403603
2016 AQP2 plasma membrane diffusion is regulated by the phosphorylation state of Ser256 in the AQP2 tetramer. Using kICS live imaging, AQP2-S256D (fully phosphorylated) diffuses faster than AQP2-S256A (non-phosphorylated). Tetramers with 2–4 phosphorylated monomers display fast diffusion similar to S256D, while tetramers with only 1 phosphorylated monomer diffuse similarly to S256A, suggesting a threshold for endocytic retention vs. membrane accumulation. k-space Image Correlation Spectroscopy (kICS) live imaging; AQP2-S256D/A phospho-mutants; mixed tetramers with defined phosphorylation stoichiometry in MDCK cells International journal of molecular sciences Medium 27801846
2006 cAMP can regulate AQP2 expression via a PKA-independent pathway. AVP activates both ERK and CREB pathways; ERK inhibition attenuates AVP-induced AQP2 upregulation while PKA inhibitors alone do not block it. Pharmacological inhibitors of PKA and ERK; immunoblotting for AQP2, ERK, and CREB in IMCD cells Biochimica et biophysica acta Medium 16844078
1997 Substitution of the mercury-sensitive cysteine (C181) in AQP2 with serine abolishes water channel function and causes retention in the endoplasmic reticulum, indicating that C181 is essential for both AQP2 routing and mercury sensitivity. In contrast, the equivalent mutation in AQP1 (C189S) does not affect function, indicating structural differences between AQP1 and AQP2. Oocyte expression of C181S and C181A AQP2 mutants; osmotic water permeability assay; mercury inhibition; immunocytochemistry and immunoblotting The American journal of physiology Medium 9321919
1998 Vasopressin-induced AQP2 translocation to the apical membrane is accompanied by increased transepithelial osmotic water permeability (Pf), and this response requires the AQP2 C-terminus for regulated trafficking. A chimera of AQP1 bearing the AQP2 C-terminus shows partial regulated water permeability; AQP1 alone shows no vasopressin-responsive trafficking. Mercury inhibits the hydroosmotic response, confirming channel-mediated water transport. LLC-PK1 cells stably transfected with AQP1, AQP2, or AQP1/AQP2 chimera; transepithelial osmotic water permeability measurement; mercury inhibition; electron microscopy The Journal of membrane biology Medium 9435270
2014 Tankyrase mediates vasopressin-induced AQP2 expression via β-catenin-mediated transcription. Tankyrase inhibition (XAV939) or siRNA knockdown attenuates dDAVP-induced AQP2 upregulation without affecting PKA activation. Tankyrase inhibition decreases dDAVP-induced phosphorylation of β-catenin at S552 and its nuclear translocation. β-catenin siRNA knockdown decreases forskolin-induced AQP2 transcription. FRET-based PKA activation imaging; XAV939 (tankyrase inhibitor); siRNA knockdown of tankyrase and β-catenin; immunoblotting; nuclear translocation assay in mpkCCDc14 cells American journal of physiology. Renal physiology Medium 25520007
2021 PDCD10-STK24/25-ERM signaling pathway regulates AQP2 vesicle trafficking and membrane abundance. Kidney tubule-specific knockout of Pdcd10 or Stk24/25 in mice causes polyuria and reduced apical membrane AQP2 and phospho-AQP2 without decreased AQP2 mRNA. This is associated with increased expression and membrane targeting of ezrin/radixin/moesin (p-ERM) proteins, impairing intracellular vesicle trafficking. Erlotinib (promoting exocytosis/inhibiting endocytosis) normalizes AQP2 membrane abundance and partially rescues water reabsorption. Kidney tubule-specific conditional KO mice; immunofluorescence; erlotinib treatment; urine output measurement; p-ERM immunoblotting JCI insight Medium 34156031
2013 AQP5 (when aberrantly expressed) directly interacts with AQP2 and impairs its cell surface localization. The AQP5/AQP2 complex partially resides in the ER/Golgi. This interaction was identified by co-immunoprecipitation, and its functional consequence (reduced AQP2 surface expression) was confirmed by cell surface biotinylation assay. Co-immunoprecipitation; cell surface biotinylation; colocalization by immunofluorescence in IMCD3, MLE-15, and 293T cells PloS one Medium 23326416
2018 CaSR signaling reduces AQP2 abundance via two mechanisms: (1) activation of p38-MAPK which phosphorylates AQP2 at Ser261, promoting ubiquitination and proteasomal degradation; (2) induction of AQP2-targeting miRNA-137. Both effects are reversed by CaSR inhibitor NPS2143 in pendrin/NCC double-knockout mice with high urinary calcium. Immunoblotting for phospho-AQP2, ubiquitinated AQP2, p38-MAPK in dKO mice; calcilytic NPS2143 treatment; miRNA-137 quantification; proteasome inhibitor FASEB journal Medium 29212817
2018 AQP2 excreted in human urine is predominantly (80%) localized to low-density exosomes. These AQP2-bearing exosomes contain ESCRT complex components and retain functional water channel activity (measured by stopped-flow light scattering), with Pf value inhibited by HgCl2. AQP2 abundance correlates with vesicle Pf. Differential ultracentrifugation of human urine; immunoprecipitation with AQP2 antibody; LC-MS/MS proteomics; stopped-flow osmotic water permeability measurement Clinical and experimental nephrology Medium 29396622
2022 MIAC micropeptide directly binds AQP2 protein in renal cell carcinoma cells. This interaction inhibits EREG/EGFR signaling and downstream PI3K/AKT and MAPK pathways, thereby inhibiting tumor progression. Binding was demonstrated by co-immunoprecipitation, affinity experiments, molecular docking, and streptavidin pulldown. Co-immunoprecipitation; affinity experiments; molecular docking; streptavidin pulldown; in vitro and in vivo tumor experiments Molecular cancer Low 36117171

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The AQP2 water channel: effect of vasopressin treatment, microtubule disruption, and distribution in neonatal rats. The Journal of membrane biology 207 7539496
2005 Distribution of AQP2 and AQP3 water channels in human tissue microarrays. Journal of molecular histology 162 15703994
2000 Localization and regulation of PKA-phosphorylated AQP2 in response to V(2)-receptor agonist/antagonist treatment. American journal of physiology. Renal physiology 159 10644653
1997 Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. The American journal of physiology 154 9140044
2006 Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proceedings of the National Academy of Sciences of the United States of America 129 16581908
2003 Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. American journal of physiology. Renal physiology 111 14519593
1998 Expression of an AQP2 Cre recombinase transgene in kidney and male reproductive system of transgenic mice. The American journal of physiology 111 9688853
2006 Increased AQP2 targeting in primary cultured IMCD cells in response to angiotensin II through AT1 receptor. American journal of physiology. Renal physiology 86 16896188
2004 Bidirectional regulation of AQP2 trafficking and recycling: involvement of AQP2-S256 phosphorylation. American journal of physiology. Renal physiology 83 15625084
2006 Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress. American journal of physiology. Cell physiology 81 17166937
2004 Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats. American journal of physiology. Renal physiology 79 15585668
1996 Expression and functional analysis of water channels in a stably AQP2-transfected human collecting duct cell line. The Journal of biological chemistry 77 8798691
2013 Aqp2-expressing cells give rise to renal intercalated cells. Journal of the American Society of Nephrology : JASN 76 23308014
2013 Actin directly interacts with different membrane channel proteins and influences channel activities: AQP2 as a model. Biochimica et biophysica acta 68 23770358
2000 The phosphatase inhibitor okadaic acid induces AQP2 translocation independently from AQP2 phosphorylation in renal collecting duct cells. Journal of cell science 66 10806109
2005 Differential regulation of AQP2 trafficking in endosomes by microtubules and actin filaments. Histochemistry and cell biology 65 16049696
2005 Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. Journal of the American Society of Nephrology : JASN 65 16120822
2001 Compensatory increase in AQP2, p-AQP2, and AQP3 expression in rats with diabetes mellitus. American journal of physiology. Renal physiology 64 11249863
2000 Recycling of AQP2 occurs through a temperature- and bafilomycin-sensitive trans-Golgi-associated compartment. American journal of physiology. Renal physiology 64 10662736
2002 Osmolality and solute composition are strong regulators of AQP2 expression in renal principal cells. American journal of physiology. Renal physiology 62 12388395
2005 Actin remodeling requires ERM function to facilitate AQP2 apical targeting. Journal of cell science 60 16046477
2022 Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma. Molecular cancer 58 36117171
2012 Functional interaction between AQP2 and TRPV4 in renal cells. Journal of cellular biochemistry 58 21938744
2005 Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. American journal of physiology. Renal physiology 58 16159898
1998 Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct. The American journal of physiology 55 9486234
2016 Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway. Nature communications 54 27892464
2013 Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2. PloS one 54 23326416
2002 Axial heterogeneity in basolateral AQP2 localization in rat kidney: effect of vasopressin. American journal of physiology. Renal physiology 54 12453871
2000 Vasopressin V(2)-receptor-dependent regulation of AQP2 expression in Brattleboro rats. American journal of physiology. Renal physiology 54 10919858
2001 AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex. American journal of physiology. Renal physiology 51 11592953
2016 Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation. International journal of nanomedicine 50 27099493
2006 cAMP regulates vasopressin-induced AQP2 expression via protein kinase A-independent pathway. Biochimica et biophysica acta 50 16844078
2012 Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2. Clinical and experimental nephrology 47 23150186
2004 Upregulation of urea transporter UT-A2 and water channels AQP2 and AQP3 in mice lacking urea transporter UT-B. Journal of the American Society of Nephrology : JASN 47 15100356
2015 Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome. American journal of physiology. Renal physiology 45 25694485
2008 AQP2 exocytosis in the renal collecting duct -- involvement of SNARE isoforms and the regulatory role of Munc18b. Journal of cell science 44 18505797
2004 Insulin potentiates AVP-induced AQP2 expression in cultured renal collecting duct principal cells. American journal of physiology. Renal physiology 44 15494547
2009 Rapid and segmental specific dysregulation of AQP2, S256-pAQP2 and renal sodium transporters in rats with LPS-induced endotoxaemia. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 43 19193739
2008 AKAP220 colocalizes with AQP2 in the inner medullary collecting ducts. Kidney international 43 19008911
2002 AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. American journal of physiology. Renal physiology 43 12388409
2020 Statins ameliorate cholesterol-induced inflammation and improve AQP2 expression by inhibiting NLRP3 activation in the kidney. Theranostics 42 32929357
2006 Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney epithelial cells: AQP2 is located in 'endocytosis-resistant' membrane domains after vasopressin treatment. Biology of the cell 42 16563128
2012 Differential, phosphorylation dependent trafficking of AQP2 in LLC-PK1 cells. PloS one 41 22403603
2011 Integrin signaling modulates AQP2 trafficking via Arg-Gly-Asp (RGD) motif. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 41 21691091
2009 Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1 receptor blockade. American journal of physiology. Renal physiology 41 19776175
2018 AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus. Nature communications 39 29650969
2017 NDFIP allows NEDD4/NEDD4L-induced AQP2 ubiquitination and degradation. PloS one 39 28931009
2005 Volume regulation in cortical collecting duct cells: role of AQP2. Biology of the cell 39 15859948
2005 Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats. American journal of physiology. Renal physiology 38 15956775
2003 Dual influence of aldosterone on AQP2 expression in cultured renal collecting duct principal cells. The Journal of biological chemistry 36 12660245
2017 Ezrin directly interacts with AQP2 and promotes its endocytosis. Journal of cell science 35 28754689
2015 Vasopressin-regulated miRNAs and AQP2-targeting miRNAs in kidney collecting duct cells. American journal of physiology. Renal physiology 35 25651560
2011 Emerging role of Akt substrate protein AS160 in the regulation of AQP2 translocation. American journal of physiology. Renal physiology 35 21511697
2015 Estradiol regulates AQP2 expression in the collecting duct: a novel inhibitory role for estrogen receptor α. American journal of physiology. Renal physiology 34 26062878
2010 Diuretic activity and kidney medulla AQP1, AQP2, AQP3, V2R expression of the aqueous extract of sclerotia of Polyporus umbellatus FRIES in normal rats. Journal of ethnopharmacology 34 20083182
1998 Acute effects of vasopressin V2-receptor antagonist on kidney AQP2 expression and subcellular distribution. The American journal of physiology 34 9691020
2022 AQP2 Promotes Astrocyte Activation by Modulating the TLR4/NFκB-p65 Pathway Following Intracerebral Hemorrhage. Frontiers in immunology 33 35386692
2021 AQP2 as a target of lycopene protects against atrazine-induced renal ionic homeostasis disturbance. Food & function 33 33960999
2004 Changes of rat kidney AQP2 and Na,K-ATPase mRNA expression in lithium-induced nephrogenic diabetes insipidus. Nephron. Experimental nephrology 33 15153756
2001 Fasting downregulates renal water channel AQP2 and causes polyuria. American journal of physiology. Renal physiology 33 11181414
2019 Renal denervation improves sodium excretion in rats with chronic heart failure: effects on expression of renal ENaC and AQP2. American journal of physiology. Heart and circulatory physiology 32 31490733
2011 AQP2 is necessary for vasopressin- and forskolin-mediated filamentous actin depolymerization in renal epithelial cells. Biology open 32 23213402
2005 Decreased expression of AQP2 and AQP4 water channels and Na,K-ATPase in kidney collecting duct in AQP3 null mice. Biology of the cell 31 15898956
2017 Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5. The Journal of biological chemistry 30 28710278
2008 Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking. Pflugers Archiv : European journal of physiology 30 18389276
2007 Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation. American journal of physiology. Renal physiology 30 18094031
1997 Closely spaced tandem arrangement of AQP2, AQP5, and AQP6 genes in a 27-kilobase segment at chromosome locus 12q13. Genomics 30 9268644
2018 AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities. Clinical and experimental nephrology 29 29396622
2017 AQP2 Abundance is Regulated by the E3-Ligase CHIP Via HSP70. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 29 29145196
2013 Excretion of urinary exosomal AQP2 in rats is regulated by vasopressin and urinary pH. American journal of physiology. Renal physiology 29 23986519
2020 AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions. Cells 28 32993088
2009 Effect of the cGMP pathway on AQP2 expression and translocation: potential implications for nephrogenic diabetes insipidus. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 28 19666909
2017 Protein phosphatase 2C is responsible for VP-induced dephosphorylation of AQP2 serine 261. American journal of physiology. Renal physiology 27 28381458
2018 Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus. Clinical and experimental nephrology 26 29478202
2016 Phosphatase inhibition increases AQP2 accumulation in the rat IMCD apical plasma membrane. American journal of physiology. Renal physiology 26 27488997
2018 Estrogen nuclear receptors affect cell migration by altering sublocalization of AQP2 in glioma cell lines. Cell death discovery 25 30345080
2015 Rosiglitazone promotes AQP2 plasma membrane expression in renal cells via a Ca-dependent/cAMP-independent mechanism. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 25 25662477
2008 Alterations of AQP2 expression in trigeminal ganglia in a murine inflammation model. Neuroscience letters 25 19014999
2008 Decreased expression of endometrial vessel AQP1 and endometrial epithelium AQP2 related to anovulatory uterine bleeding in premenopausal women. Menopause (New York, N.Y.) 24 18463544
2018 Protein-protein interactions in AQP regulation - biophysical characterization of AQP0-CaM and AQP2-LIP5 complex formation. Faraday discussions 23 29972182
2015 Extracellular pH affects phosphorylation and intracellular trafficking of AQP2 in inner medullary collecting duct cells. American journal of physiology. Renal physiology 23 25651562
2014 Tankyrase-mediated β-catenin activity regulates vasopressin-induced AQP2 expression in kidney collecting duct mpkCCDc14 cells. American journal of physiology. Renal physiology 23 25520007
1997 Importance of the mercury-sensitive cysteine on function and routing of AQP1 and AQP2 in oocytes. The American journal of physiology 23 9321919
2018 CaSR signaling down-regulates AQP2 expression via a novel microRNA pathway in pendrin and NaCl cotransporter knockout mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 29212817
2016 AQP2 Plasma Membrane Diffusion Is Altered by the Degree of AQP2-S256 Phosphorylation. International journal of molecular sciences 22 27801846
2018 Zhen-wu-tang attenuates Adriamycin-induced nephropathy via regulating AQP2 and miR-92b. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 30551379
2017 The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment. Journal of cellular and molecular medicine 21 28326667
2016 Renal phenotype in Bardet-Biedl syndrome: a combined defect of urinary concentration and dilution is associated with defective urinary AQP2 and UMOD excretion. American journal of physiology. Renal physiology 21 27488999
2009 Role of AQP2 during apoptosis in cortical collecting duct cells. Biology of the cell 21 18717646
2021 Dysregulation of Principal Cell miRNAs Facilitates Epigenetic Regulation of AQP2 and Results in Nephrogenic Diabetes Insipidus. Journal of the American Society of Nephrology : JASN 20 33727367
2003 Reduced renal expression of AQP2, p-AQP2 and AQP3 in haemorrhagic shock-induced acute renal failure. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20 14605277
2022 AQP2 trafficking in health and diseases: an updated overview. The international journal of biochemistry & cell biology 19 35798273
2021 Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury. American journal of physiology. Renal physiology 19 33427060
2018 Steviol slows renal cyst growth by reducing AQP2 expression and promoting AQP2 degradation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 29524884
2016 Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway. Medical science monitor basic research 19 27980322
1998 Reconstitution of a regulated transepithelial water pathway in cells transfected with AQP2 and an AQP1/AQP2 hybrid containing the AQP2-C terminus. The Journal of membrane biology 19 9435270
2015 Polarized Trafficking of AQP2 Revealed in Three Dimensional Epithelial Culture. PloS one 18 26147297
2012 Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus. Endocrine 18 22644838
2011 Bilateral ureteral obstruction induces early downregulation and redistribution of AQP2 and phosphorylated AQP2. American journal of physiology. Renal physiology 18 21525134
2021 Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting. JCI insight 17 34156031

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