Affinage

Showing KIRREL1 — NEPH1 is a alias.

KIRREL1

Kin of IRRE-like protein 1 · UniProt Q96J84

Length
757 aa
Mass
83.5 kDa
Annotated
2026-06-10
34 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIRREL1/NEPH1 is a transmembrane immunoglobulin-superfamily adhesion receptor that is required to maintain the structural integrity of the glomerular filtration barrier in podocytes (PMID:11416156). At the slit diaphragm it localizes to the lateral margins of podocyte foot processes (PMID:12865409, PMID:12646566) and assembles a heterodimeric, fishnet-like lattice with Nephrin: its extracellular Ig domains mediate glycosylation-dependent cis- and trans-heterodimerization with Nephrin (it does not engage in homophilic interactions in foot processes) [PMID:12646566, PMID:12660326, PMID:bio_10.1101_2025.09.24.678239], while its cytoplasmic tail couples to the slit-diaphragm scaffold through a C-terminal motif and residues Lys-761/Tyr-762 that bind the ZO-1 PDZ domain (PMID:12865409, PMID:22262837) and through podocin (PMID:12424224). Upon engagement KIRREL1 is phosphorylated on cytoplasmic tyrosines (including Y637/Y638) by the Src-family kinase Fyn, which recruits Grb2 to drive actin polymerization in cooperation with Nephrin-bound Nck and also recruits Csk to attenuate ERK signaling (PMID:17923684, PMID:18258597); Fyn-dependent phosphorylation likewise stabilizes the KIRREL1–ZO-1 interaction and membrane localization, a coupling that is acutely lost during ischemic and ATP-depletion injury and restored on recovery (PMID:18922801). Membrane delivery and turnover of KIRREL1 depend on direct, actin-dependent binding to the motor protein Myo1c (PMID:21402783, PMID:27044863), and failure of mutant KIRREL1 to reach the podocyte membrane causes steroid-resistant nephrotic syndrome in patients with homozygous KIRREL1 mutations (PMID:31472902). Beyond the kidney, KIRREL1 acts as a direct receptor for HGF, binding through its extracellular domain and undergoing MET-independent phosphorylation that promotes podocyte repair (PMID:34391780), and it functions as an upstream positive regulator of the Hippo pathway by recruiting SAV1 and LATS1/2 to cell–cell contacts to promote LATS1/2 activation and YAP/TAZ suppression within a TEAD-dependent negative feedback loop, restraining tumorigenesis in liver and biliary models (PMID:35177623, PMID:36044856, PMID:35704761). KIRREL1/NEPH1 is also expressed at neuronal synapses and dendrites, where it binds CASK and is required for neurite branching (PMID:16874800, PMID:39049046).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Established that NEPH1 is physiologically essential for the glomerular filtration barrier, framing it as a slit-diaphragm component rather than an incidental podocyte protein.

    Evidence Gene-trap knockout mice with EM and proteinuria readouts

    PMID:11416156

    Open questions at the time
    • Did not define molecular partners or the biochemical basis of the phenotype
    • No mechanism for how loss leads to foot process effacement
  2. 2003 High

    Resolved where and with what NEPH1 acts at the slit diaphragm, showing it localizes to the slit-diaphragm insertion and forms a Nephrin-linked, ZO-1-coupled adhesion complex whose integrity sustains the barrier.

    Evidence Immunogold EM, Co-IP, in vivo antibody perturbation, cell fractionation

    PMID:12646566 PMID:12660326 PMID:12865409

    Open questions at the time
    • Did not establish the intracellular signaling consequences of complex assembly
    • Trans- vs cis-orientation of Nephrin–NEPH1 not fully resolved at this stage
  3. 2002 High

    Identified podocin as a cytoplasmic NEPH1 partner and a tyrosine-dependent binding motif, linking NEPH1 to other slit-diaphragm scaffolding and to AP-1 transcriptional output.

    Evidence Co-IP, mutagenesis, transcriptional reporter assay

    PMID:12424224

    Open questions at the time
    • Functional significance of AP-1 activation in podocytes unresolved
    • Tec-family kinase identity not pinned down
  4. 2008 High

    Defined the kinase-substrate logic of NEPH1 signaling, showing Fyn phosphorylates specific cytoplasmic tyrosines (Y637/Y638) to recruit Grb2 and Csk and drive actin polymerization, connecting adhesion to cytoskeletal remodeling.

    Evidence In vitro kinase assay, mass fingerprinting, mutagenesis, glomerular pulldown, actin polymerization assay

    PMID:17923684 PMID:18258597

    Open questions at the time
    • Quantitative contribution of NEPH1 vs Nephrin to actin output not separated
    • In vivo relevance of ERK attenuation unclear
  5. 2008 High

    Showed the NEPH1–ZO-1 interaction is dynamically regulated by Fyn phosphorylation and disrupted by injury, providing a molecular mechanism for slit-diaphragm disassembly and recovery during ischemia.

    Evidence In vivo rat ischemia model, ATP depletion, Co-IP, immunofluorescence, Fyn kinase assay

    PMID:18922801

    Open questions at the time
    • Upstream signal triggering Fyn reactivation during recovery not identified
  6. 2011 High

    Identified Myo1c as the motor delivering NEPH1 (and Nephrin) to the membrane, explaining how the slit-diaphragm complex is trafficked and assembled.

    Evidence Co-IP, dominant-negative and siRNA, surface fractionation, wound and TEER assays

    PMID:21402783

    Open questions at the time
    • Regulation of Myo1c-dependent delivery not defined
    • Cargo selectivity mechanism unknown
  7. 2012 High

    Provided structural definition of the NEPH1 cytoplasmic domain and its ZO-1 interface, identifying Lys-761/Tyr-762 as critical contacts and rendering the interaction structurally tractable.

    Evidence SWAXS, circular dichroism, mutagenesis pulldowns

    PMID:22262837

    Open questions at the time
    • No high-resolution atomic structure of the full complex
    • Phospho-regulation not captured structurally
  8. 2016 High

    Structurally characterized the NEPH1–Myo1c interaction and demonstrated by FRAP that Myo1c mediates vesicular movement and membrane turnover of NEPH1.

    Evidence SAXS, mutagenesis, in vitro binding, live-cell FRAP

    PMID:27044863

    Open questions at the time
    • Coupling of motor activity to specific trafficking routes unresolved
  9. 2014 Medium

    Demonstrated that maintaining membrane NEPH1 and its signaling protects podocytes from injury, establishing NEPH1 stabilization as a candidate protective strategy.

    Evidence Protein transduction, lipid raft fractionation, permeability assays, zebrafish injury model

    PMID:24554715

    Open questions at the time
    • Single lab
    • Mechanism by which Neph1CD retains the protein in rafts not fully defined
  10. 2017 Medium

    Showed the NEPH1–ZO-1 interface is druggable, with the small molecule isodesmosine enhancing binding and conferring injury resistance in vitro and in vivo.

    Evidence Computational screening, binding assay, podocyte permeability assay, mouse and zebrafish injury models

    PMID:28935902

    Open questions at the time
    • Single lab
    • Direct target engagement specificity of ISD not orthogonally confirmed
  11. 2017 Low

    Reported CD80 (B7-1) as an extracellular NEPH1 partner associated with actin derangement, hinting at an immune-injury link.

    Evidence Pulldown in HEK293 overexpression, immunofluorescence co-localization

    PMID:29022109

    Open questions at the time
    • Single pulldown in overexpression system without reciprocal validation
    • No endogenous interaction or in vivo evidence
  12. 2019 Medium

    Linked KIRREL1 directly to human disease, showing homozygous mutations cause steroid-resistant nephrotic syndrome through defective membrane trafficking of mutant protein.

    Evidence Patient genetics, immunofluorescence localization of mutant vs WT KIRREL1

    PMID:31472902

    Open questions at the time
    • Single study
    • Trafficking step that fails not mechanistically defined
  13. 2009 High

    Extended NEPH1 function beyond scaffolding by showing it regulates BK/Slo1 channel surface expression and current in podocytes and neurons.

    Evidence Reciprocal endogenous Co-IP, GST pulldown, surface biotinylation, electrophysiology, siRNA

    PMID:19794150

    Open questions at the time
    • Directionality of regulation differs between cell types and is unexplained
    • Structural basis of Slo1 binding not defined
  14. 2021 High

    Revealed NEPH1 (and Nephrin) as a direct HGF receptor undergoing MET-independent, SHP-2-reversible phosphorylation that promotes podocyte repair, recasting NEPH1 as a ligand-responsive signaling receptor.

    Evidence SPR with purified recombinant proteins, modeling, cell and Drosophila nephrocyte assays

    PMID:34391780

    Open questions at the time
    • Downstream effectors of HGF-induced NEPH1 phosphorylation not fully mapped
    • Relative in vivo contribution vs MET signaling unclear
  15. 2022 High

    Defined a distinct role for KIRREL1 as an upstream positive regulator of the Hippo pathway, recruiting SAV1 and LATS1/2 to cell-cell contacts to activate LATS and suppress YAP/TAZ within a TEAD-dependent feedback loop, with tumor-suppressive consequences.

    Evidence Co-IP, KO and transgenic mouse models, CRISPR screens, LATS kinase and TEAD reporter assays, liver regeneration and cholangiocarcinoma models

    PMID:35177623 PMID:35704761 PMID:36044856

    Open questions at the time
    • How adhesion-based KIRREL1 engagement is transduced to LATS activation mechanistically unresolved
    • Connection between slit-diaphragm and Hippo roles not reconciled
  16. 2023 Medium

    Reported a pro-tumorigenic, PI3K/AKT/mTOR-linked role for KIRREL1 in gastric cancer, contrasting with its Hippo tumor-suppressive function and indicating context-dependent outputs.

    Evidence Lentiviral knockdown/overexpression, western blot, pharmacological pathway modulation

    PMID:37909722

    Open questions at the time
    • No direct binding to PI3K components shown
    • Single lab
    • Reconciliation with Hippo tumor-suppressor role absent
  17. 2024 Medium

    Established transcriptional control of Neph1 by the homeodomain factor PRRXL1 and a functional requirement for Neph1 in neurite branching, deepening its neuronal role.

    Evidence ChIP, in situ hybridization, loss-of-function, neurite morphometry

    PMID:39049046

    Open questions at the time
    • Single lab
    • Molecular mechanism of Neph1 in neurite branching unresolved
  18. 2025 Medium

    Resolved the native slit diaphragm as a conserved Nephrin–NEPH1 heterodimeric fishnet lattice with species-specific spacing, providing the supramolecular architecture underlying the barrier.

    Evidence Cryo-electron tomography of native human and mouse kidney tissue with atomic model fitting (preprint)

    PMID:bio_10.1101_2025.09.24.678239

    Open questions at the time
    • Preprint, not peer-reviewed
    • Single study
    • Dynamics of lattice remodeling not captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KIRREL1's adhesion/scaffolding function at cell-cell contacts is mechanistically transduced into Hippo (LATS) activation, and how its opposing tumor-suppressive versus pro-proliferative outputs are determined by cellular context, remain unresolved.
  • No mechanism linking extracellular engagement to LATS activation
  • Context-dependent tumor roles not reconciled
  • Integration of kidney, neuronal, and Hippo functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 2
Partners
FYNGRB2LATS1MYO1CNPHS1NPHS2SAV1TJP1
Complex memberships
slit diaphragm (Nephrin-NEPH1 fishnet lattice)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NEPH1 knockout mice develop proteinuria and podocyte foot process effacement, establishing that NEPH1 is required for maintaining the structural integrity of the glomerular filtration barrier in podocytes. Gene trap knockout mice; electron microscopy; proteinuria assay Molecular and cellular biology High 11416156
2002 NEPH1 directly interacts with the C-terminal domain of podocin via a conserved binding motif; mutation of a centrally located tyrosine residue dramatically reduces NEPH1-podocin affinity. NEPH1 also triggers AP-1 activation requiring Tec family kinases. Co-immunoprecipitation; mutagenesis; transcriptional reporter assay FASEB journal High 12424224
2003 NEPH1 localizes to the glomerular slit diaphragm (confirmed by immunogold EM) and directly interacts with nephrin (via extracellular segments) and ZO-1 (via ZO-1 PDZ domains interacting with the cytoplasmic tail of Neph1). Neph1 forms dimers and multimers. Disrupting the Neph1-nephrin interaction in vivo by injecting subnephritogenic doses of both antibodies causes proteinuria and dramatically reduces ZO-1 protein levels without altering ZO-1 mRNA. Immunogold electron microscopy; co-immunoprecipitation; in vivo antibody injection; western blot The Journal of clinical investigation High 12865409
2003 Neph1 localizes exclusively to the lateral margins of podocyte foot processes at the slit diaphragm insertion. Neph1 and Nephrin form cis heterodimers via their cytoplasmic domains, and interactions between extracellular domains of Nephrin with itself and with Neph1 were detected. Neph1 does not engage in homophilic interactions. Immunogold electron microscopy; co-immunoprecipitation; cell fractionation (detergent-resistant membrane) The Journal of biological chemistry High 12646566
2003 The extracellular Ig domains of NEPH1 mediate both homodimerization and heterodimerization with nephrin; as few as two Ig domains are sufficient for binding. These interactions are strictly dependent on post-translational glycosylation (bacterially expressed unglycosylated protein fails to bind). Co-immunoprecipitation; Ig-fusion pulldown; truncation analysis; glycosylation-deficient expression Journal of the American Society of Nephrology High 12660326
2006 Neph1 is expressed in the developing mammalian brain and localizes to dendritic shafts and synaptic sites. Neph1 interacts with the PDZ domain of the synaptic scaffolding protein CASK via its cytoplasmic tail, suggesting a role in synaptogenesis. In situ hybridization; immunohistochemistry; immunogold EM; co-immunoprecipitation The Journal of comparative neurology Medium 16874800
2007 Upon engagement, Neph1 is phosphorylated on specific tyrosine residues by the Src family kinase Fyn, which recruits the adaptor Grb2. This Grb2 recruitment is necessary for Neph1-induced actin polymerization at the plasma membrane. Neph1 and Nephrin directly interact and cooperate by juxtaposing Grb2 and Nck1/2 at the membrane to augment actin polymerization efficiency. Phosphorylation assay; co-immunoprecipitation; dominant-negative and siRNA knockdown; actin polymerization assay; mutagenesis Molecular and cellular biology High 17923684
2008 Fyn phosphorylates the cytoplasmic domain of Neph1 at multiple tyrosines (including Y637 and Y638) both in vitro and in intact cells. Phosphorylated Neph1 specifically binds adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner (from glomerular lysates). Neph1 attenuates Fyn-elicited ERK activation, requiring intact Grb2-SH2 binding motif. Phosphorylation of Y637 is upregulated in vivo in podocyte injury models. In vitro kinase assay; peptide mass fingerprinting; site-directed mutagenesis; GST pulldown from rat glomerular lysates; co-immunoprecipitation The Journal of biological chemistry High 18258597
2008 Renal ischemia induces rapid loss of interaction between slit diaphragm proteins Neph1 and ZO-1, with redistribution of both proteins from cell membrane to cytoplasm. Recovery from ATP-depletion injury restores Neph1 tyrosine phosphorylation (mediated by Fyn), which is required for re-establishing Neph1-ZO-1 binding and their co-localization at the membrane. Fyn-mediated Neph1 phosphorylation significantly increases Neph1-ZO-1 binding. In vivo rat ischemia model; co-immunoprecipitation; cell culture ATP depletion; immunofluorescence; Fyn kinase assay The Journal of biological chemistry High 18922801
2009 Neph1 interacts with large-conductance Ca2+-activated K+ (BK/Slo1) channels via all three extreme C-terminal Slo1 splice variants, as shown by reciprocal Co-IP from endogenous podocyte and neuron proteins and GST pulldown. Co-expression of Neph1 with Slo1 suppresses steady-state Slo1 surface expression in HEK293T cells. Conversely, siRNA knockdown of Neph1 in ciliary ganglion neurons increases surface Slo1 and BK current, while knockdown in podocytes decreases Slo1 surface expression and BK current. Reciprocal co-immunoprecipitation from endogenous proteins; GST pulldown; cell surface biotinylation; whole-cell electrophysiology; siRNA knockdown; confocal microscopy American journal of physiology. Cell physiology High 19794150
2011 Neph1 and Nephrin can trans-interact across cells to induce cell adhesion (demonstrated in L fibroblasts lacking endogenous adhesion). Neph1 alone can induce cell adhesion. Trans-interaction of nephrin with Neph1 (or Neph3) is associated with down-regulation of nephrin tyrosine phosphorylation. L fibroblast cell adhesion assay; co-immunoprecipitation; phosphorylation analysis The Biochemical journal Medium 21306299
2011 Motor protein Myo1c directly interacts with Neph1 in an actin-dependent manner and is required for targeting Neph1 to the podocyte cell membrane. Expression of dominant-negative Myo1c or siRNA depletion of Myo1c significantly reduces membrane localization of Neph1 and nephrin. Myo1c knockdown also impairs cell migration and tight junction formation. Co-immunoprecipitation in vivo and in vitro; dominant-negative expression; siRNA knockdown; cell surface fractionation; wound assay; transepithelial electric resistance Molecular and cellular biology High 21402783
2012 The solution structure of the Neph1 cytoplasmic domain (Neph1-CD) was determined by SWAXS (radius of gyration 21.3 Å, max dimension 70 Å). A structural model of the Neph1-CD·ZO-1-PDZ1 complex was constructed; beyond the C-terminal Thr-His-Val motif, residues Lys-761 and Tyr-762 in Neph1 are critical for ZO-1 binding (individual alanine mutations abolished binding). Small/wide angle X-ray scattering (SWAXS); circular dichroism; in vitro and in vivo pulldown with mutagenesis The Journal of biological chemistry High 22262837
2014 Inhibiting Neph1 signaling by transducing its cytoplasmic domain (Neph1CD) into podocytes reduces puromycin aminonucleoside (PAN)-induced Neph1 phosphorylation, retains Neph1 in lipid raft fractions, maintains Neph1 at the membrane, and protects against cytoskeletal damage and albumin leakage. Maintaining high membrane levels of Neph1 via chimeric overexpression increases podocyte resistance to PAN injury. Protein transduction; lipid raft fractionation; immunofluorescence; transepithelial permeability assay; zebrafish in vivo injury model The Journal of biological chemistry Medium 24554715
2016 The full-length Myo1c adopts an extended S-shaped conformation in solution; Neph1 binds to the C-terminal tail of Myo1c without inducing significant conformational change. A critical residue in Neph1 required for Myo1c binding was identified; point mutation abolished the interaction in vitro and in live cells. FRAP analysis confirmed Myo1c mediates intracellular vesicular movement and membrane turnover of Neph1. Small angle X-ray scattering (SAXS); mutagenesis; in vitro binding assay; live-cell imaging; fluorescence recovery after photobleaching (FRAP) Molecular and cellular biology High 27044863
2017 The Neph1-ZO-1 protein-protein interaction interface contains a druggable pocket involving both proteins. The small molecule isodesmosine (ISD) enhances Neph1 cytoplasmic domain–ZO-1 binding in vitro and in vivo, and ISD-treated podocytes are resistant to injury-induced transepithelial permeability loss. Mouse and zebrafish experiments confirm ISD protects from injury-induced renal damage. Computational structural screening; biochemical binding assay; in vitro podocyte permeability assay; mouse and zebrafish injury models Scientific reports Medium 28935902
2017 CD80 (B7-1) interacts with Neph1 via their extracellular domains, as established by pulldown assay in HEK293 cells co-transfected with both proteins. CD80 overexpression in podocytes co-localizes with Neph1 and causes actin derangement. Co-immunoprecipitation/pulldown in HEK293 cells; immunofluorescence co-localization in podocytes Clinical and experimental nephrology Low 29022109
2019 Homozygous mutations in KIRREL1 in patients with steroid-resistant nephrotic syndrome result in mutant KIRREL1 proteins that fail to localize to the podocyte cell membrane, indicating defective membrane trafficking. Patient genetics; immunofluorescence localization of mutant vs wild-type KIRREL1 in podocytes Kidney international Medium 31472902
2021 NEPHRIN and NEPH1 are novel receptor proteins for hepatocyte growth factor (HGF), binding HGF directly through their extracellular domains (confirmed by surface plasmon resonance with purified recombinant proteins; NEPHRIN Kd ~20-fold higher affinity than NEPH1). HGF binding leads to phosphorylation of NEPHRIN and NEPH1 independently of the MET receptor. SHP-2 (PTPN11) mediates dephosphorylation of these proteins. HGF-induced phosphorylation promotes podocyte repair. Surface plasmon resonance with purified baculovirus-expressed recombinant proteins; molecular modeling; cell culture and Drosophila nephrocyte functional assays The Journal of biological chemistry High 34391780
2022 KIRREL1 physically interacts with SAV1 and recruits SAV1 to cell-cell contact sites, thereby activating the Hippo pathway. Knockout of KIRREL1 increases YAP activity in neighboring cells. During liver regeneration in mice, KIRREL1 knockout enhances hepatic YAP activity, hepatocyte reprogramming, and biliary epithelial cell proliferation. Co-immunoprecipitation; knockout mouse model; in vivo liver regeneration assay; YAP activity reporter Nature communications High 35177623
2022 KIRREL1 interacts with both SAV1 and LATS1/2, promoting LATS1/2 activation by MST1/2 (Hippo kinases), thereby suppressing YAP/TAZ oncoproteins. YAP/TAZ in turn directly induce KIRREL1 expression in a TEAD1-4-dependent manner, constituting a negative feedback loop. Transgenic expression of KIRREL1 blocks tumorigenesis in a mouse intrahepatic cholangiocarcinoma model. Co-immunoprecipitation; LATS kinase activity assay; CRISPR screen; TEAD reporter assay; transgenic mouse tumor model Cell reports High 36044856
2022 KIRREL binds directly to SAV1 to activate the Hippo tumor suppressor pathway. KIRREL loss markedly promotes tumor growth in vivo. This was discovered through an in vivo CRISPR screen of cell surface proteins and a separate CRISPR screen using a Hippo pathway reporter. In vivo CRISPR proliferation screen; Hippo pathway reporter CRISPR screen; direct binding assay Proceedings of the National Academy of Sciences Medium 35704761
2023 KIRREL1 knockdown inhibits proliferation and angiogenesis of gastric cancer cells; overexpression promotes them. These effects are mediated through the PI3K/AKT/mTOR pathway: KIRREL1 silencing represses P-PI3K, P-AKT, P-mTOR, HIF-1α, and VEGF, while overexpression stimulates them. The AKT agonist IGF-1 and inhibitor LY294002 reverse these effects. Lentiviral knockdown/overexpression; western blot; pharmacological pathway inhibition/activation Journal of cellular and molecular medicine Medium 37909722
2024 PRRXL1 homeodomain transcription factor directly regulates Neph1 transcription by binding to four intronic regions of the Neph1 gene (identified by ChIP), preventing premature Neph1 expression in dorsal horn superficial laminae at E14.5. Loss-of-function experiments show Neph1 is required for neurite branching, especially at distal neurites. Chromatin immunoprecipitation (ChIP); in situ hybridization; loss-of-function (Neph1 KO or knockdown); neurite morphometry Neural development Medium 39049046
2025 Cryo-electron tomography of human kidney tissue resolves the slit diaphragm as a fishnet-like lattice with crisscrossing strands at ~90°. An atomic model based on the Nephrin-Neph1 heterodimer fits the structure, with ~9 nm spacing in humans (vs 12.3 nm in mice and 15 nm in Drosophila), indicating the SD is a conserved heterodimeric fishnet assembly. Cryo-electron tomography of native human and mouse kidney tissue; atomic model fitting bioRxivpreprint Medium bio_10.1101_2025.09.24.678239

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Molecular and cellular biology 337 11416156
2002 NEPH1 defines a novel family of podocin interacting proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 179 12424224
2003 Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability. The Journal of clinical investigation 172 12865409
2003 Nephrin and Neph1 co-localize at the podocyte foot process intercellular junction and form cis hetero-oligomers. The Journal of biological chemistry 152 12646566
2009 Sns and Kirre, the Drosophila orthologs of Nephrin and Neph1, direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes. Development (Cambridge, England) 138 19515699
2003 Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1. Journal of the American Society of Nephrology : JASN 137 12660326
2007 Neph1 cooperates with nephrin to transduce a signal that induces actin polymerization. Molecular and cellular biology 125 17923684
2011 Motor protein Myo1c is a podocyte protein that facilitates the transport of slit diaphragm protein Neph1 to the podocyte membrane. Molecular and cellular biology 77 21402783
2008 Ischemic injury to kidney induces glomerular podocyte effacement and dissociation of slit diaphragm proteins Neph1 and ZO-1. The Journal of biological chemistry 72 18922801
2008 Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2. The Journal of biological chemistry 67 18258597
2006 Neuronal expression and interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis. The Journal of comparative neurology 48 16874800
2008 Dissociation of NEPH1 from nephrin is involved in development of a rat model of focal segmental glomerulosclerosis. American journal of physiology. Renal physiology 45 18715943
2014 Slit diaphragm protein Neph1 and its signaling: a novel therapeutic target for protection of podocytes against glomerular injury. The Journal of biological chemistry 40 24554715
2010 Recognition of pre- and postsynaptic neurons via nephrin/NEPH1 homologs is a basis for the formation of the Drosophila retinotopic map. Development (Cambridge, England) 40 20724453
2022 Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites. Nature communications 31 35177623
2022 Transmembrane protein KIRREL1 regulates Hippo signaling via a feedback loop and represents a therapeutic target in YAP/TAZ-active cancers. Cell reports 25 36044856
2019 Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome. Kidney international 23 31472902
2011 Trans-interaction of nephrin and Neph1/Neph3 induces cell adhesion that associates with decreased tyrosine phosphorylation of nephrin. The Biochemical journal 23 21306299
2009 Neph1 regulates steady-state surface expression of Slo1 Ca(2+)-activated K(+) channels: different effects in embryonic neurons and podocytes. American journal of physiology. Cell physiology 22 19794150
2022 Integrated screens uncover a cell surface tumor suppressor gene KIRREL involved in Hippo pathway. Proceedings of the National Academy of Sciences of the United States of America 21 35704761
2017 Targeting Neph1 and ZO-1 protein-protein interaction in podocytes prevents podocyte injury and preserves glomerular filtration function. Scientific reports 21 28935902
2017 Interaction of CD80 with Neph1: a potential mechanism of podocyte injury. Clinical and experimental nephrology 21 29022109
2021 Molecular and structural basis of olfactory sensory neuron axon coalescence by Kirrel receptors. Cell reports 14 34731636
2017 Loss of Kirrel family members alters glomerular structure and synapse numbers in the accessory olfactory bulb. Brain structure & function 14 28815295
2012 Solution structure analysis of cytoplasmic domain of podocyte protein Neph1 using small/wide angle x-ray scattering (SWAXS). The Journal of biological chemistry 13 22262837
2021 Phosphorylation of slit diaphragm proteins NEPHRIN and NEPH1 upon binding of HGF promotes podocyte repair. The Journal of biological chemistry 12 34391780
2014 Angiotensin II type 1 receptor blockade ameliorates proteinuria in puromycin aminonucleoside nephropathy by inhibiting the reduction of NEPH1 and nephrin. Journal of nephrology 11 25298195
2014 Neph1 is reduced in primary focal segmental glomerulosclerosis, minimal change nephrotic syndrome, and corresponding experimental animal models of adriamycin-induced nephropathy and puromycin aminonucleoside nephrosis. Nephron extra 11 25404935
2023 KIRREL promotes the proliferation of gastric cancer cells and angiogenesis through the PI3K/AKT/mTOR pathway. Journal of cellular and molecular medicine 9 37909722
2016 Structural Analysis of the Myo1c and Neph1 Complex Provides Insight into the Intracellular Movement of Neph1. Molecular and cellular biology 9 27044863
2013 Identification and characterization of novel Kirrel isoform during myogenesis. Physiological reports 8 24303129
2026 Anti-nephrin, anti-podocin and anti-Kirrel1 antibodies: biological challenges and clinical implications. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 5 40815258
2017 KIRREL is differentially expressed in adipose tissue from 'fertil+' and 'fertil-' cows: in vitro role in ovary? Reproduction (Cambridge, England) 3 29170164
2024 Neph1 is required for neurite branching and is negatively regulated by the PRRXL1 homeodomain factor in the developing spinal cord dorsal horn. Neural development 1 39049046

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