| 2000 |
Nectin-3alpha forms a cis-homodimer and undergoes Ca2+-independent trans-homo-interaction to cause homophilic cell-cell adhesion; it also undergoes trans-hetero-interaction with nectin-1 or nectin-2 (but does not form cis-heterodimers with them). Nectin-3alpha co-localizes with nectin-2 at cadherin-based adherens junctions and interacts with afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. |
Cell-based adhesion assays, co-immunoprecipitation, immunofluorescence colocalization |
The Journal of biological chemistry |
High |
10744716
|
| 2000 |
Nectin-3/PRR3 carries the C-terminal A/EXYV consensus motif and interacts in vivo with both long and short isoforms of afadin via this motif. |
In vivo co-immunoprecipitation, sequence analysis |
Gene |
Medium |
11024295
|
| 2002 |
The trans-hetero-interaction of nectin-3 with nectin-1 is mediated through V-to-V domain contacts (KD ~1 nM), with C domains contributing to increased affinity. The minimal nectin-3 binding region on nectin-1 was mapped to the C-C'-C"-D beta-strands of the V domain using chimeric nectin1/PVR receptors. |
Surface plasmon resonance binding assays, chimeric receptor domain-swap experiments, competition assays with blocking antibodies and HSV-1 glycoprotein D |
The Journal of biological chemistry |
High |
12011057
|
| 2003 |
Necl-5/Tage4 (later renamed nectin-like molecule-5) heterophilically trans-interacts with nectin-3 but not homophilically, and this trans-interaction enhances motility of V12Ras-NIH3T3 cells. Unlike nectins, Tage4/Necl-5 does not bind afadin. |
Cell-based ligand binding assays, cell motility assays, co-immunoprecipitation |
The Journal of biological chemistry |
Medium |
12740392
|
| 2003 |
Nectin-3 binds CD155 (PVR) and its mouse homologue Tage4 in cell-based ligand binding assays. Coculture of nectin-3- and CD155-expressing cells led to CD155-dependent recruitment of nectin-3 to cell-cell contacts. CD155 co-distributes with alpha(v) integrin microdomains, suggesting a trans-interaction between cell-cell (nectin) and cell-matrix (integrin/CD155) adhesion systems at junctions. |
Cell-based ligand binding assays, immunofluorescence colocalization, heterologous coculture system |
The Journal of biological chemistry |
Medium |
12759359
|
| 2004 |
Necl-5 enhances cell migration in an integrin alpha(V)beta(3)-dependent, nectin-3-independent manner when cells are not in contact; Necl-5 colocalizes with integrin alpha(V)beta(3) at leading edges. Necl-5-enhanced migration requires activation of Cdc42 and Rac small GTPases. |
Mutant Necl-5 constructs in L fibroblasts and NIH3T3 cells, integrin inhibitor/activator assays, dominant-negative mutants, small GTPase activation assays |
The Journal of biological chemistry |
Medium |
14871893
|
| 2004 |
Upon Necl-5/nectin-3 heterophilic trans-interaction, afadin, E-cadherin, and catenins are recruited to the nectin-3 side (not the Necl-5 side) of the contact site, facilitating adherens junction formation. A monoclonal antibody blocking Necl-5/nectin-3 interaction inhibited E-cadherin-based AJ formation. |
Stable cell lines expressing Necl-5, nectin-3, and E-cadherin; immunofluorescence; blocking antibody experiments |
Genes to cells |
Medium |
15330856
|
| 2005 |
Nectin-1 and nectin-3 heterophilic trans-interaction is required for establishing apex-apex adhesion between pigment and non-pigment cell layers of the ciliary epithelia; nectin-1-/- and nectin-3-/- mice both show microphthalmia with separation of this contact layer, while apicolateral junctions are unaffected. |
Genetic knockout mice (nectin-1-/- and nectin-3-/-), immunofluorescence and immunoelectron microscopy |
Development |
High |
15728677
|
| 2005 |
Upon cell-cell contact, Necl-5 is down-regulated from the cell surface via clathrin-dependent endocytosis initiated by its interaction with nectin-3; this down-regulation reduces cell movement and proliferation, representing a mechanism for contact inhibition. |
Cell-surface down-regulation assays, clathrin inhibitor experiments, nectin-3-dependent coculture assays |
The Journal of cell biology |
High |
16216929
|
| 2006 |
Nectin-3 localizes asymmetrically to the spermatid side of Sertoli-spermatid junctions and its heterophilic trans-interaction with nectin-2 (on Sertoli cells) is essential for spermatid development. Nectin-3-/- mice are male-infertile with distorted sperm nuclei, abnormal mitochondrial distribution, and mislocalized nectin-2; wild-type stem cell transplantation partially rescues these defects. |
Genetic knockout mice (nectin-3-/-), immunolocalization, spermatogenic stem cell transplantation rescue experiment |
Genes to cells |
High |
16923130
|
| 2012 |
CADM1 on mast cells mediates attachment to dorsal root ganglion (DRG) neurites and subsequent calcium responses via heterophilic binding to nectin-3 expressed on DRG neurons; a neutralizing antibody to nectin-3 inhibited both mast cell attachment and calcium signaling. |
Neutralizing antibody blocking assay, co-culture attachment assays, calcium imaging |
Journal of neuroimmunology |
Medium |
22703826
|
| 2012 |
sFRP1 regulates spermatid adhesion and spermiation by suppressing phosphorylation of FAK (Tyr397), which in turn reduces phosphorylation and promotes retention of nectin-3 at the apical ectoplasmic specialization. In vivo administration of recombinant sFRP1 delayed spermiation with concurrent nectin-3 retention; overexpression in Sertoli-germ cell coculture confirmed FAK-nectin-3 phosphorylation axis. |
In vivo recombinant protein administration, lentiviral overexpression in coculture, Western blotting for phospho-FAK and phospho-nectin-3 |
FASEB journal |
Medium |
23073828
|
| 2013 |
Hippocampal nectin-3 is necessary for stress effects on spatial memory and dendritic spine density. Acute and chronic stress reduce hippocampal nectin-3 levels via CRH-CRHR1 signaling (not glucocorticoid receptor). Knockdown of hippocampal nectin-3 caused spatial memory deficits and spine loss; restoration of nectin-3 rescued early-life stress effects on memory and spine density in adulthood. |
AAV-mediated knockdown and overexpression, CRHR1 knockout mice, CRH-overexpressing transgenic mice, fear conditioning and spatial memory tasks, dendritic spine analysis |
Nature neuroscience |
High |
23644483
|
| 2013 |
Nectin-3 expressed on T lymphocytes trans-interacts with nectin-2 on high endothelial venules; blocking either nectin-3 (on lymphocytes) or nectin-2 (on ECs) with monoclonal antibodies inhibits lymphocyte transendothelial migration in vitro. |
Soluble nectin-3 binding assays, blocking monoclonal antibodies, transendothelial migration assay |
PloS one |
Medium |
24116228
|
| 2014 |
MMP-9 proteolytically cleaves nectin-3 in the perisynaptic CA1 region following chronic restraint stress; this process involves NMDA receptor activation and is responsible for stress-induced social and cognitive alterations. Nectin-3 reduction was specific to CA1, not CA3. |
Gelatinase activity assays, MMP-9 inhibition, NMDA receptor antagonism, immunohistochemistry, behavioral assays |
Nature communications |
High |
25232752
|
| 2014 |
In Nectin-3-deficient mice, hair cells aberrantly contact each other and form abnormal junctions; this leads to disturbed hair bundle orientation and morphology, abnormal kinocilium positioning, and mislocalization of cadherin-catenin complexes and polarity proteins Pals1 and Par-3 specifically in the aberrantly attached (not unattached) HCs. |
Nectin-3 knockout mice, immunofluorescence, confocal and electron microscopy |
Development |
High |
24381198
|
| 2015 |
Crystal structure of the afadin PDZ domain (AFPDZ) in complex with the nectin-3 C-terminal peptide revealed that the last three C-terminal amino acids of nectin-3 (containing two hydrophobic residues of the class II motif) are sufficient for AFPDZ binding, and binding induces a ~2.5 Å-wider ligand-binding groove in AFPDZ compared to unliganded structures. |
X-ray crystallography of AFPDZ-nectin-3 fusion protein complex |
Protein science |
High |
25534554
|
| 2015 |
Nectin-3 sialylation is regulated by TGFBR2 signaling in colon cancer cells; upon TGFBR2 reconstitution, nectin-3 loses sialic acid incorporation, identifying nectin-3 as a glycoprotein target of TGFBR2-dependent glycome regulation. |
RMCE-based TGFBR2 reconstitution, Click-It chemistry for sialic acid labeling, mass spectrometry |
Protein science |
Medium |
26177744
|
| 2016 |
Nectin-3 is present in rat uterine epithelial cells as three isoforms (80, 60, 32 kDa) and redistributes from basal cytoplasmic localization to cell junctions at the time of implantation (day 6); this junctional localization is regulated by progesterone. At implantation, nectin-3 localizes to the tight junction but does not interact with occludin or l-afadin. |
Immunofluorescence, Western blotting, co-immunoprecipitation, progesterone manipulation |
Reproductive sciences |
Medium |
27217376
|
| 2017 |
Nectin-3 protein in spermatids is internalized at tubulobulbar complexes (clathrin/actin-based junction-internalizing structures) at Sertoli-spermatid junctions; nectin-3 labeling occurs at junctions, tubulobulbar complex bulbs, and associated double-membrane vesicles, with Rab5 associating with bulbs before scission. |
Pre-embedding immunoelectron microscopy with Rab5, EEA1, and nectin-3 antibodies |
Anatomical record |
Medium |
28176461
|
| 2017 |
AAV-mediated knockdown of nectin-3 in dentate gyrus neurons impaired long-term spatial memory and temporal order memory, increased density of immature doublecortin+ and calretinin+ neurons but decreased calbindin immunoreactivity, indicating nectin-3 modulates differentiation/maturation of adult-born granule cells. Selective nectin-3 knockdown in new DG neurons via retrovirus reduced thin dendritic spines. |
AAV-mediated knockdown, retroviral labeling of newborn neurons, immunohistochemistry for neurogenesis markers, behavioral testing |
Translational psychiatry |
High |
28872640
|
| 2020 |
ZNF582 directly regulates transcription of nectin-3 (and NRXN3) as shown by ChIP-seq and ChIP-qPCR; restoration or abrogation of nectin-3 reversed the tumor suppressor effect of ZNF582 on NPC migration and invasion in vitro and in vivo. |
ChIP-seq, ChIP-qPCR, luciferase reporter assay, rescue/epistasis experiments with nectin-3 overexpression/knockdown |
Cancer communications |
Medium |
33038291
|
| 2020 |
AAV-mediated knockdown of nectin-3 in mouse medial prefrontal cortex (mPFC) during adolescence reproduced chronic stress-induced impairments in social recognition and spatial working memory, and reduced dendritic complexity and spine density; membrane localization of nectin-3 was significantly correlated with behavioral performance. |
AAV-mediated knockdown, behavioral testing, dendritic morphology analysis, membrane fractionation |
Neuroscience bulletin |
Medium |
32385776
|
| 2020 |
Precise levels of nectin-3 in visual cortex layer 2/3 neurons regulate dendritic spine density during synaptogenesis. Knockdown increased dendritic spine density at P21/P35; overexpression decreased it. Overexpression of nectin-3 lacking its afadin-binding domain caused an even greater decrease in spine density on basal dendrites, indicating the afadin-binding domain is important for nectin-3's role in spine formation. |
In utero electroporation with shRNA knockdown and full-length/truncated overexpression constructs; spine density analysis at multiple developmental timepoints |
Neural development |
Medium |
33160402
|
| 2023 |
Nectin-3, previously characterized as an adherens junction protein, is also localized to the brush border of colonocytes and can serve as a cell surface receptor for Clostridioides difficile toxin B (TcdB) on colonic epithelial cells. |
Immunofluorescence microscopy on colonic tissue, receptor localization studies |
mBio |
Medium |
37747247
|
| 2024 |
Knockdown of dorsal CA1 nectin-3 impaired object recognition memory in adolescent female mice, while overexpression of dorsal CA1 nectin-3 reversed early-life stress-induced recognition memory deficits. Systemic CRHR1 antagonism (antalarmin) upregulated hippocampal nectin-3 levels and rescued memory deficits, placing nectin-3 downstream of CRHR1 signaling. |
AAV-mediated knockdown and overexpression, pharmacological CRHR1 antagonism, novel object recognition behavioral testing |
Neuroscience bulletin |
Medium |
39395912
|
| 2025 |
PCP signaling (via Vangl2) regulates the junctional localization of Nectin-3 in cochlear supporting cells; loss of Nectin-3 partially phenocopies SGNII peripheral afferent turning defects seen in Vangl2 mutants. Epistasis analysis indicates Nectin-3 and Rac1 act in the same genetic pathway downstream of PCP to control SGNII axon guidance, with Nectin-3 likely providing a cell adhesion function for afferent turning. |
Genetic loss-of-function (Nectin-3 and Rac1 conditional knockouts), epistasis with Vangl2 mutants, immunofluorescence of junctional protein localization |
Development |
Medium |
40207531
|