Affinage

AQP2

Aquaporin-2 · UniProt P41181

Length
271 aa
Mass
28.8 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AQP2 is the principal vasopressin-regulated water channel of the renal collecting duct, functioning as the rate-limiting step for urinary water reabsorption. In unstimulated cells, AQP2 tetramers reside in Rab11-positive subapical vesicles and constitutively recycle through clathrin-mediated endocytosis; vasopressin binding to V2R activates adenylate cyclase→cAMP→PKA, which phosphorylates AQP2 at Ser256 (necessary but not sufficient for apical targeting), inactivates RhoA to promote actin depolymerization, and drives SNARE-mediated (VAMP2/3, syntaxin-3, SNAP23) fusion of AQP2 vesicles with the apical membrane (PMID:10644653, PMID:12640036, PMID:18505797, PMID:14519593). Retrieval from the membrane is facilitated by a direct ezrin–AQP2 interaction that promotes clathrin-dependent endocytosis, while lysosomal degradation requires NDFIP1/2-dependent recruitment of NEDD4/NEDD4L E3 ligases for AQP2 ubiquitination, and phosphorylation at Ser256 allosterically reduces LIP5 binding to oppose lysosomal sorting (PMID:28754689, PMID:28931009, PMID:28710278). Loss-of-function mutations cause nephrogenic diabetes insipidus—recessive forms through ER misrouting of otherwise functional channels, dominant forms through hetero-oligomeric trapping of wild-type AQP2—and collecting-duct-specific knockout produces severe polyuria, confirming AQP2 as essential and non-redundant for renal water conservation (PMID:9048343, PMID:16120822, PMID:16581908).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1995 High

    Establishing that AQP2 undergoes regulated redistribution from cytoplasmic vesicles to the apical membrane in response to vasopressin answered the fundamental question of how collecting duct water permeability is acutely controlled and identified microtubule-dependent vesicle trafficking as the underlying mechanism.

    Evidence Immunofluorescence and immunogold EM in Brattleboro rats ± vasopressin and colchicine

    PMID:7539496

    Open questions at the time
    • Motor proteins driving microtubule-dependent transport not identified
    • Signal transduction pathway between V2R and vesicle movement undefined
  2. 1997 High

    Demonstrating that recessive NDI mutations produce functional water channels that are ER-retained, and that V2R activates AQP2 transcription via CREB/AP1, established that both trafficking competence and transcriptional regulation are critical for AQP2 function, and that disease arises from misrouting rather than channel dysfunction.

    Evidence Xenopus oocyte water permeability with NDI mutants (A147T, T126M, N68S); AQP2 promoter-reporter assays with V2R activation in LLC-PK1 cells

    PMID:9048343 PMID:9140044

    Open questions at the time
    • Chaperone interactions responsible for ER quality control of AQP2 mutants not identified
    • Relative contribution of transcriptional vs. trafficking regulation to water reabsorption in vivo unclear
  3. 2000 High

    Identification of Ser256 as the PKA phosphorylation site required for vasopressin-induced apical targeting, alongside discovery of constitutive AQP2 recycling and PGE2-mediated retrieval independent of S256 dephosphorylation, revealed that AQP2 membrane abundance is governed by the balance of regulated exocytosis and phosphorylation-independent endocytosis.

    Evidence Phospho-S256-specific antibodies with immunoEM in rat kidney; temperature-block and bafilomycin experiments in LLC-PK1 cells; PGE2 retrieval assays in rat IMCD

    PMID:10644653 PMID:10662736 PMID:10710543

    Open questions at the time
    • Identity of kinases/phosphatases acting on other C-terminal serines unknown
    • Endocytic machinery components mediating retrieval not defined
  4. 2003 High

    Showing that cAMP/PKA inhibits RhoA via phosphorylation (promoting RhoGDI association and actin depolymerization) and that blocking clathrin-mediated endocytosis causes S256-independent AQP2 membrane accumulation established that regulated exocytosis requires cytoskeletal remodeling while constitutive recycling is clathrin-dependent.

    Evidence RhoA-GTP pull-down and RhoA-RhoGDI co-IP in CD8 cells; dominant-negative dynamin and mβCD in LLC-PK1/IMCD cells with S256A mutant controls

    PMID:12640036 PMID:14519593

    Open questions at the time
    • Specific Rho-GEFs and GAPs involved not identified
    • How S256 phosphorylation intersects with endocytic machinery unknown
  5. 2005 High

    Mapping the AQP2 intracellular itinerary through Rab11-positive storage compartments and EEA1-positive early endosomes, together with demonstrating moesin-dependent actin remodeling during exocytosis, defined the vesicular sorting pathway and the ERM-actin axis as a trafficking checkpoint.

    Evidence Double immunolabeling, Rab11 siRNA, nocodazole/latrunculin pharmacology in MDCK cells; moesin subcellular redistribution and peptide competitor in renal cells

    PMID:16046477 PMID:16049696

    Open questions at the time
    • Which Rab effectors mediate Rab11-to-apical delivery unclear
    • Functional link between moesin phosphorylation state and AQP2 exocytosis not fully resolved
  6. 2006 High

    Collecting-duct-specific AQP2 knockout producing lethal polyuria, together with identification of calcineurin and angiotensin II/AT1R as additional regulators of AQP2 trafficking, established AQP2 as non-redundant for water balance and revealed cAMP-independent signaling inputs.

    Evidence Cre/loxP conditional knockout mice; CnAα-null mice and cyclosporin A; AngII/candesartan/PKC inhibitors in primary IMCD cells

    PMID:16581908 PMID:16735444 PMID:16896188

    Open questions at the time
    • Calcineurin substrates relevant to AQP2 trafficking not identified
    • How PKC integrates with PKA-dependent phosphorylation at S256 unresolved
  7. 2008 High

    Identification of VAMP2/3, syntaxin-3, SNAP23, and Munc18b as the SNARE machinery for AQP2 vesicle fusion, and AKAP220 as a PKA-recruiting scaffold on AQP2 vesicles, provided the molecular basis for both the final membrane fusion step and compartmentalized PKA signaling.

    Evidence Co-IP of SNAREs with AQP2 vesicles and siRNA knockdown with biotinylation in MCD4 cells; yeast two-hybrid and co-expression phosphorylation assay for AKAP220

    PMID:18505797 PMID:19008911

    Open questions at the time
    • AKAP220 interaction awaits reciprocal co-IP validation
    • How Munc18b release is triggered upon cAMP stimulation unknown
    • Specific SNARE regulatory steps (NSF, α-SNAP involvement) not characterized
  8. 2012 Medium

    Systematic phospho-mutant analysis revealed that S256, S261, S264, and S269 differentially regulate AQP2 internalization kinetics and membrane retention, while TRPC3 was identified as a co-trafficking partner that inserts with AQP2 into the apical membrane, expanding AQP2's role beyond water transport.

    Evidence Cold-block/rewarming assays with phospho-mutants in LLC-PK1 cells; TRPC3-AQP2 co-IP and dominant-negative TRPC3 with calcium flux in M1/IMCD-3 cells

    PMID:17699554 PMID:22403603

    Open questions at the time
    • Kinases responsible for S264 and S269 phosphorylation in vivo not definitively identified
    • Physiological significance of TRPC3 co-trafficking for calcium homeostasis in principal cells unclear
  9. 2017 High

    Discovery that NDFIP1/2 adaptors recruit NEDD4/NEDD4L to ubiquitinate AQP2 for lysosomal degradation, that phospho-S256 allosterically reduces LIP5 binding to oppose lysosomal targeting, that ezrin directly binds AQP2 to facilitate endocytosis, and that PP2C dephosphorylates S261 defined the molecular logic of AQP2 downregulation and degradation.

    Evidence Membrane Y2H, siRNA of NEDD4/NDFIP in mpkCCD; MST binding with phosphomimetic AQP2 peptides; recombinant ezrin pulldown and shRNA in collecting duct cells; PP2C inhibitor sanguinarine with phospho-specific antibodies

    PMID:28381458 PMID:28710278 PMID:28754689 PMID:28931009

    Open questions at the time
    • Ubiquitination sites on AQP2 not mapped
    • Whether ezrin and NEDD4 pathways are sequential or parallel not resolved
    • Structural basis for phosphorylation-dependent LIP5 affinity change unknown
  10. 2018 High

    Demonstration that AKAP-PKA disruptor FMP-API-1 bypasses V2R to phosphorylate AQP2 and concentrate urine in vivo, and that Wnt5a/calcineurin provides a cAMP-independent AQP2 trafficking pathway, opened pharmacological strategies for treating nephrogenic diabetes insipidus.

    Evidence FMP-API-1 in cortical CD cells and V2R-inhibited mice with urine osmolality; Wnt5a/arachidonic acid in CD cells and NDI mouse model

    PMID:27892464 PMID:29650969

    Open questions at the time
    • Off-target effects of AKAP disruption on other renal PKA substrates not characterized
    • Wnt5a receptor and downstream calcineurin substrates in principal cells not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structural basis for phosphorylation-dependent conformational changes in the AQP2 C-terminus, the complete ubiquitination site map, the identity of specific Rab effectors mediating apical delivery, and whether pharmacological targeting of the Wnt5a/calcineurin or AKAP-disruptor pathways is therapeutically viable for NDI.
  • No high-resolution structure of full-length AQP2 with C-terminal regulatory domain
  • Ubiquitination sites not mapped
  • Rab11 effectors for apical delivery not identified
  • Clinical translation of AKAP disruptors or calcineurin activators untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 2
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-9609507 Protein localization 4 R-HSA-382551 Transport of small molecules 2
Partners
EZRNDFIP1NEDD4LRAB11ASNAP23STX3TRPC3VAMP2
Complex memberships
AQP2 homotetramer

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 AQP2 relocates from cytoplasmic vesicles to the apical plasma membrane of collecting duct principal cells following vasopressin treatment, and this apical targeting depends on intact microtubules (colchicine disruption scatters AQP2 throughout the cytoplasm). Immunofluorescence and immunogold electron microscopy in Brattleboro rats with/without vasopressin and colchicine treatment The Journal of membrane biology High 7539496
2000 Vasopressin-induced AQP2 trafficking to the apical plasma membrane requires PKA-mediated phosphorylation at Ser256; phospho-AQP2 (pS256) is present in both the apical membrane and intracellular vesicles, and V2 receptor blockade causes near-complete loss of apical pS256-AQP2. Phosphorylation state-specific antibodies, immunoelectron microscopy, immunoblotting in rat kidney with DDAVP or V2R antagonist treatment American journal of physiology. Renal physiology High 10644653
1997 Vasopressin acting via the adenylate cyclase-coupled V2 receptor activates AQP2 gene transcription through phosphorylation of CREB and induction of c-Fos, which together bind the CRE and AP1 elements in the AQP2 promoter. Transfection of human AQP2 promoter in LLC-PK1 cells; CREB phosphorylation and c-Fos expression assays with V2R activation The American journal of physiology High 9140044
1997 Autosomal recessive NDI-associated AQP2 missense mutations (A147T, T126M, N68S) produce proteins that are functional water channels in Xenopus oocytes but are misrouted to the ER rather than the plasma membrane, establishing that misrouting (not loss of channel function) is the primary cause of recessive NDI. Xenopus oocyte water permeability assays, immunoblotting, immunocytochemistry of oocyte lysates Journal of the American Society of Nephrology High 9048343
2000 Prostaglandin E2 antagonizes vasopressin-induced AQP2 plasma membrane translocation by promoting retrieval of AQP2 to intracellular vesicles independently of AQP2 dephosphorylation at Ser256. Differential centrifugation, phosphorylation state-specific AQP2 antibody, incubation of rat renal inner medulla with AVP and PGE2 American journal of physiology. Renal physiology High 10710543
2000 AQP2 constitutively recycles between intracellular vesicles and the cell surface via a trans-Golgi-associated compartment; this recycling is blocked by 20°C incubation or bafilomycin A1 (H+-ATPase inhibitor), with AQP2 accumulating in a perinuclear compartment that colocalizes with clathrin but not giantin. Temperature block experiments, bafilomycin treatment, colocalization with organelle markers in LLC-PK1 cells American journal of physiology. Renal physiology High 10662736
2003 cAMP-induced AQP2 translocation to the apical membrane is accompanied by RhoA inhibition via PKA-mediated RhoA phosphorylation (on serine), which increases RhoA association with RhoGDI, thereby promoting actin depolymerization required for vesicle fusion. Selective RhoA pull-down (GTP-bound RhoA), cell fractionation, co-immunoprecipitation of RhoA and RhoGDI, forskolin stimulation of CD8 renal cells Journal of cell science High 12640036
2003 Inhibition of clathrin-mediated endocytosis (by dominant-negative dynamin-2/K44A or methyl-β-cyclodextrin) causes rapid, constitutive plasma membrane accumulation of AQP2 independently of Ser256 phosphorylation, demonstrating that AQP2 constitutively recycles and that phosphorylation at S256 is required for regulated (vasopressin-dependent) but not constitutive membrane insertion. Dominant-negative dynamin expression, cholesterol depletion with mβCD, cell-surface biotinylation, FITC-dextran endocytosis assay in LLC-PK1 and IMCD cells American journal of physiology. Renal physiology High 14519593
2004 S256 phosphorylation of AQP2 is necessary but not sufficient for plasma membrane expression; active PKA is required for sustained apical AQP2 localization. PGE2 and dopamine induce AQP2 endocytosis independently of AQP2 dephosphorylation at S256. PKA inhibitor H-89 treatment, AQP2-S256D phosphomimetic mutant, dopamine/PGE2 treatment, confocal microscopy in MDCK-C7 cells and rat kidney inner medullary slices American journal of physiology. Renal physiology High 15625084
2005 Dominant NDI caused by AQP2-R254L (which destroys the PKA consensus site adjacent to S256) results from loss of vasopressin-mediated phosphorylation at S256; AQP2-R254L is a functional water channel but is retained intracellularly and, when co-expressed, retains wild-type AQP2 in intracellular vesicles. Xenopus oocyte water permeability, MDCK cell co-expression, immunofluorescence, phospho-specific immunoblotting, S256D rescue experiment Journal of the American Society of Nephrology High 16120822
2005 AQP2 is stored in Rab11-positive subapical compartments prior to apical translocation; after endocytosis, AQP2 moves to EEA1-positive early endosomes and back to the Rab11 compartment. Microtubules maintain the subapical compartment distribution; actin filaments regulate trafficking from early endosomes to the storage compartment. Rab11 depletion by RNAi impairs AQP2 retention in the storage compartment. Double immunolabeling, siRNA knockdown of Rab11, pharmacological disruption of microtubules (nocodazole, colcemid) and actin (cytochalasin D, latrunculin B) in MDCK cells Histochemistry and cell biology High 16049696
2005 ERM protein moesin is required for actin remodeling during AQP2 vesicular trafficking to the apical membrane; forskolin causes moesin redistribution to the cell cortex and reduction of phospho-moesin, and a moesin peptide blocking F-actin binding mimics forskolin effects including AQP2 translocation. Subcellular fractionation, confocal microscopy, Triton X-100 extraction of cytoskeletal proteins, moesin peptide introduction in renal cells Journal of cell science Medium 16046477
2005 Human AQP2 adopts a typical aquaporin fold as a tetramer; 4.5 Å 2D electron crystallography structure reveals the cytosolic N and C termini form contacts between stacked double-layer sheets. 2D crystallization of recombinant human AQP2, atomic force microscopy, electron crystallography Journal of molecular biology Medium 15922355
1998 Cytoplasmic dynein and dynactin colocalize with AQP2-bearing vesicles in rat renal collecting duct principal cells, consistent with a role of the dynein motor complex in vasopressin-regulated AQP2 vesicle trafficking. Immunoblotting, immunoisolation of AQP2 vesicles with anti-AQP2 antibody, quantitative double immunogold electron microscopy The American journal of physiology Medium 9486234
2006 AQP2 in the collecting duct (CD) is essential for body water balance; conditional knockout mice lacking AQP2 only in CD (but retaining it in connecting tubule) show 10-fold increased urine output and severely decreased urine osmolality that cannot be compensated by other mechanisms. Global AQP2 knockout is lethal postnatally. Cre/loxP conditional knockout (Hoxb7-Cre for CD-specific, EIIa-Cre for global), metabolic cage measurements, immunohistochemistry Proceedings of the National Academy of Sciences High 16581908
2006 Loss of calcineurin Aα results in decreased vasopressin-mediated phosphorylation of AQP2 and failure of AQP2 to accumulate in the apical membrane, causing nephrogenic diabetes insipidus; calcineurin is present in IMCD vesicles and required for normal intracellular AQP2 trafficking. CnAα null mice and cyclosporin A treatment, immunoblotting for phospho-AQP2, subcellular fractionation, urine concentration tests Journal of cell science High 16735444
2006 Angiotensin II promotes AQP2 targeting to the plasma membrane of IMCD cells through AT1 receptor activation; this effect involves cAMP elevation and PKC activity and potentiates dDAVP-induced AQP2 membrane targeting. Immunofluorescence microscopy, immunoblotting for phospho-AQP2, cAMP measurement, candesartan (AT1 blocker) and PKC inhibitor treatment in primary cultured IMCD cells American journal of physiology. Renal physiology High 16896188
2008 AQP2 vesicle fusion to the apical membrane is mediated by SNARE proteins VAMP2, VAMP3, syntaxin-3, and SNAP23; Munc18b acts as a negative regulator of SNARE complex formation. Knockdown of any of these SNAREs inhibits AQP2 apical fusion, while Munc18b knockdown causes 7-fold increase in AQP2 membrane fusion without stimulation. Co-immunoprecipitation of SNARE proteins with AQP2 vesicles, siRNA knockdown, apical surface biotinylation in MCD4 renal cells Journal of cell science High 18505797
2008 AKAP220 binds AQP2 (identified by yeast two-hybrid screen) and colocalizes with AQP2 in the cytosol of inner medullary collecting ducts; AKAP220 co-expression increases forskolin-mediated phosphorylation of AQP2, suggesting it recruits PKA to AQP2-bearing vesicles. Yeast two-hybrid screen, double immunofluorescence, immunoelectron microscopy, co-expression phosphorylation assay in COS cells Kidney international Medium 19008911
2008 Annexin-2 is required for cAMP-induced AQP2 exocytosis; forskolin causes annexin-2 redistribution to lipid rafts at the plasma membrane, and an annexin-2 N-terminal peptide that blocks p11 binding inhibits AQP2-vesicle fusion to plasma membranes in vitro and prevents osmotic water permeability increase in intact cells. Cell fractionation, lipid raft analysis, in vitro vesicle-plasma membrane fusion fluorescence assay, annexin-2 peptide introduction in renal cells Pflugers Archiv Medium 18389276
2011 AQP2 directly interacts with integrin β1 via an RGD domain in its external C-loop; RGD-containing peptides increase AQP2 membrane expression in the absence of vasopressin through cAMP- or calcium-dependent pathways. Co-immunoprecipitation of AQP2 and integrin β1 in renal tissue and MCD4 cells, confocal microscopy, cell surface biotinylation, FRET-based cAMP measurement, calcium imaging Cellular physiology and biochemistry Medium 21691091
2011 AS160, a Rab GAP protein and Akt substrate, regulates AQP2 trafficking; dDAVP stimulates AS160 phosphorylation via PI3K/Akt, and siRNA knockdown of AS160 causes increased AQP2 plasma membrane expression without hormonal stimulation. siRNA knockdown, immunocytochemistry, cell surface biotinylation, phospho-Akt and phospho-AS160 immunoblotting in M-1 and mpkCCDc14 cells American journal of physiology. Renal physiology Medium 21511697
2011 Vasopressin/forskolin-mediated F-actin depolymerization is dependent on AQP2 expression; cells lacking AQP2 do not show VP/FK-mediated F-actin depolymerization, and siRNA knockdown of AQP2 significantly reduces this response. F-actin quantification, immunofluorescence, siRNA knockdown of AQP2 in MDCK and LLC-PK1 cells with varying AQP2 expression levels Biology open Medium 23213402
2012 TRPC3 physically associates with AQP2 (co-immunoprecipitation) and co-localizes with AQP2 in intracellular vesicles; vasopressin causes co-insertion of TRPC3 and AQP2 into the apical membrane, and TRPC3 mediates transepithelial Ca2+ flux in principal cells. Co-immunoprecipitation of TRPC3 and AQP2 from kidney medulla and M1/IMCD-3 cells, immunofluorescence, dominant-negative TRPC3, 45Ca2+ flux assay American journal of physiology. Renal physiology High 17699554
2012 AQP2 interacts with TRPV4, and the presence of AQP2 enables TRPV4 activation by hypotonicity; TRPV4 translocation to the plasma membrane is required for the AQP2-dependent regulatory volume decrease response. Calcium imaging, RVD measurement, ruthenium red block, TRPV4 expression and plasma membrane translocation assays in WT-RCCD1 vs. AQP2-RCCD1 cells Journal of cellular biochemistry Medium 21938744
2013 AQP5 directly interacts with AQP2 and impairs AQP2 cell surface localization; the AQP5/AQP2 complex partially resides in the ER/Golgi. Co-immunoprecipitation, cell surface biotinylation assay, colocalization, luciferase reporter assay in IMCD3, MLE-15, and 293T cells PloS one Medium 23326416
2017 NEDD4 and NEDD4L E3 ubiquitin ligases mediate ubiquitination and degradation of AQP2, but require NDFIP1 or NDFIP2 as adaptors to connect them to AQP2; PY-motif-lacking NDFIP variants fail to support ubiquitination. Membrane yeast two-hybrid (NDFIP2-AQP2 interaction), siRNA knockdown of NEDD4, NEDD4L, NDFIP1, NDFIP2 in mpkCCD cells; ubiquitination and degradation assays in HEK293 cells PloS one High 28931009
2017 AQP2 phosphorylation allosterically controls its interaction with the lysosomal trafficking protein LIP5; non-phosphorylated AQP2 binds LIP5 with highest affinity, while phosphomimetic S256E shows the greatest reduction in LIP5 affinity, linking phosphorylation state to lysosomal targeting. Far-Western blot, microscale thermophoresis, CD spectroscopy, phosphomimetic AQP2 mutants (S256E, S261E, S264E, T269E) The Journal of biological chemistry High 28710278
2017 Ezrin directly interacts with AQP2 C-terminus through its N-terminal FERM domain; this interaction facilitates AQP2 endocytosis, as ezrin knockdown increases membrane AQP2 and reduces endocytosis. Vasopressin causes redistribution of both ezrin and AQP2 to the apical membrane. Co-IP with anti-AQP2 antibody (proteomics), co-IP with anti-ezrin antibody, pulldown with purified recombinant full-length and FERM-domain ezrin, shRNA knockdown, immunofluorescence in collecting duct cells Journal of cell science High 28754689
2017 PP2C (protein phosphatase 2C) is responsible for vasopressin-induced dephosphorylation of AQP2 at Ser261; this dephosphorylation is independent of S256 phosphorylation and does not acutely regulate AQP2 membrane trafficking. Phosphatase inhibitors (sanguinarine for PP2C, okadaic acid for PP2A, cyclosporine for PP2B), phospho-specific AQP2 antibodies, AQP2-S256A mutant in renal cells and kidney tissue American journal of physiology. Renal physiology High 28381458
2016 Wnt5a regulates AQP2 protein expression, phosphorylation, and apical membrane trafficking via calcineurin signaling (independently of cAMP/PKA); calcineurin activator arachidonic acid produces vasopressin-like effects on AQP2 trafficking and increases urine osmolality in an NDI mouse model. Wnt5a treatment of collecting duct cells and NDI mouse model, calcineurin inhibitor/activator experiments, cAMP measurement, PKA activity assay, urine osmolality measurement Nature communications High 27892464
2018 Inhibition of AKAP-PKA interactions by FMP-API-1 increases free PKA activity, phosphorylates AQP2, and increases AQP2 membrane targeting and urine osmolality in vivo to the same extent as vasopressin, bypassing V2R mutations. cAMP/PKA activity assays in cortical collecting duct cells, AQP2 phosphorylation immunoblotting, urine osmolality measurement in V2R-inhibited mice Nature communications High 29650969
2014 Tankyrase-mediated β-catenin signaling is required for vasopressin-induced AQP2 expression; tankyrase inhibition (XAV939) or β-catenin siRNA knockdown attenuates dDAVP-induced AQP2 upregulation and reduces nuclear translocation of phospho-β-catenin (S552), without affecting PKA activation. Tankyrase inhibitor (XAV939), siRNA knockdown of tankyrase and β-catenin, FRET-based PKA activity, nuclear translocation assay, luciferase reporter in mpkCCDc14 cells American journal of physiology. Renal physiology Medium 25520007
2013 Hsp70 plays a role in AQP2 trafficking to the apical plasma membrane; Hsp70-2 knockdown attenuates forskolin-induced AQP2 apical membrane targeting and reduces AQP2 phosphorylation at Ser256. siRNA knockdown of Hsp70-2, cell surface biotinylation, immunoblotting for pS256-AQP2, luciferase reporter assay for Hsp70-2 promoter in mpkCCDc14 cells American journal of physiology. Renal physiology Medium 23303413
2021 The PDCD10-STK24/25 complex regulates AQP2 membrane targeting; mice deficient in Pdcd10 or Stk24/25 in kidney tubules develop polyuria with decreased AQP2 in the apical membrane, associated with increased p-ERM expression that impairs vesicle trafficking. Erlotinib treatment normalizes AQP2 membrane abundance. Conditional knockout mice, immunofluorescence, immunoblotting, Erlotinib treatment rescue experiment JCI insight Medium 34156031
2012 Phosphorylation at S256 and S269 both contribute to retention of AQP2 at the plasma membrane; S256D mutations slow internalization while S261A and S269D mutations slow development of intracellular accumulation. Differentially phosphorylated AQP2 mutants show distinct recycling kinetics but similar colocalization with Rab11, clathrin, and other markers. 20°C cold block internalization assay, rewarming assay, colocalization with vesicular markers in LLC-PK1 cells expressing AQP2 phospho-mutants PloS one Medium 22403603
2016 The degree of S256 phosphorylation in the AQP2 tetramer controls plasma membrane diffusion speed; tetramers with 2–4 phosphorylated monomers diffuse faster than those with 0–1 phosphorylated monomers, which may determine retention time in the membrane vs. endocytosis. k-space Image Correlation Spectroscopy (kICS) of AQP2-S256D/S256A mixed-tetramer constructs in live cells International journal of molecular sciences Medium 27801846
1997 Substitution of the mercury-sensitive Cys181 in AQP2 abolishes plasma membrane targeting and causes ER retention, unlike the equivalent mutation in AQP1 (C189S) which does not affect routing, indicating structural differences between AQP1 and AQP2 at this position. Xenopus oocyte water permeability assays, immunocytochemistry, immunoblotting with AQP2-C181S and AQP1-C189S mutants The American journal of physiology Medium 9321919
1999 AQP2 interactome identified by chemical cross-linking and LC-MS/MS in native rat IMCD cells reveals multiple Rab proteins (Rab1a, Rab2a, Rab5b, Rab5c, Rab7a, Rab11a, Rab11b, Rab14, Rab17) as AQP2-interacting proteins involved in membrane trafficking. Chemical cross-linking, anti-AQP2 immunoprecipitation, LC-MS/MS proteomics in rat IMCD American journal of physiology. Cell physiology Medium 29046292

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
1997 New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels. Journal of the American Society of Nephrology : JASN 130 9048343
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 128 16581908
2003 Inhibition of endocytosis causes phosphorylation (S256)-independent plasma membrane accumulation of AQP2. American journal of physiology. Renal physiology 111 14519593
2000 Prostaglandin E(2) interaction with AVP: effects on AQP2 phosphorylation and distribution. American journal of physiology. Renal physiology 111 10710543
1998 Expression of an AQP2 Cre recombinase transgene in kidney and male reproductive system of transgenic mice. The American journal of physiology 109 9688853
2003 cAMP-induced AQP2 translocation is associated with RhoA inhibition through RhoA phosphorylation and interaction with RhoGDI. Journal of cell science 106 12640036
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
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
2013 Actin directly interacts with different membrane channel proteins and influences channel activities: AQP2 as a model. Biochimica et biophysica acta 67 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
2012 Functional interaction between AQP2 and TRPV4 in renal cells. Journal of cellular biochemistry 58 21938744
2007 Vasopressin-induced membrane trafficking of TRPC3 and AQP2 channels in cells of the rat renal collecting duct. American journal of physiology. Renal physiology 58 17699554
2005 Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus. American journal of physiology. Renal physiology 58 16159898
2005 The 4.5 A structure of human AQP2. Journal of molecular biology 56 15922355
1998 Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct. The American journal of physiology 55 9486234
2022 Micropeptide MIAC inhibits the tumor progression by interacting with AQP2 and inhibiting EREG/EGFR signaling in renal cell carcinoma. Molecular cancer 54 36117171
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
2016 Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway. Nature communications 53 27892464
2013 Aqp5 is a new transcriptional target of Dot1a and a regulator of Aqp2. PloS one 53 23326416
2007 Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney. American journal of physiology. Renal physiology 53 17376764
1997 Alteration in water channel AQP-2 by removal of AVP stimulation in collecting duct cells of dehydrated rats. The American journal of physiology 52 9124394
2016 Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation. International journal of nanomedicine 49 27099493
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
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