| 2024 |
C1ql2 directly interacts with a specific splice variant of neurexin-3, Nrxn3(25b+), at hippocampal mossy fiber-CA3 synapses. This C1ql2-Nrxn3(25b+) interaction regulates synaptic vesicle recruitment and long-term potentiation. Disruption of this interaction (via non-binding C1ql2 mutant or dentate gyrus-specific Nrxn3 deletion) recapitulates the Bcl11b and C1ql2 mutant synaptic phenotypes, placing Nrxn3(25b+) downstream of the Bcl11b/C1ql2 transcriptional pathway. |
In vivo mouse genetics (conditional KO), in vitro electrophysiology (LTP recording), expression of non-binding C1ql2 mutant, direct interaction assay, epistasis analysis |
eLife |
High |
38358390
|
| 2024 |
Nrxn3, functioning as a presynaptic adhesion molecule, is essential for ribbon-synapse maturation in hair cells. Loss of Nrxn3 in both mouse and zebrafish leads to significantly fewer intact ribbon synapses; in zebrafish, initial pre- and postsynapse numbers are normal but synapses fail to pair over time, resulting in postsynapse loss. A 60% loss of ribbon synapses in nrxn3 zebrafish mutants dramatically reduces pre- and postsynaptic responses. |
Mouse and zebrafish genetic KO, confocal imaging of synaptic markers, electrophysiology (pre- and postsynaptic response recording), behavioral assays (acoustic startle response) |
Development (Cambridge, England) |
High |
38410471 39254120
|
| 2002 |
NRXN3 is expressed not only in neurons but also in heart, lung, pancreas, placenta, liver, and kidney. Heart-specific splicing variants of NRXN3 were identified and characterized, and cardiac isoforms of NRXN3 likely participate in a complex involving dystroglycan and extracellular matrix proteins involved in intercellular connections. |
RT-PCR, tissue expression panel, characterization of alternative splicing variants |
Biochemical and biophysical research communications |
Medium |
12379233
|
| 2013 |
FoxQ1 directly binds the NRXN3 promoter region and suppresses its transcriptional activity, leading to downregulation of NRXN3 expression. This FoxQ1-mediated repression of NRXN3 promotes glioma cell proliferation and migration, as depletion of FoxQ1 reduces these capacities. |
Chromatin immunoprecipitation (ChIP), luciferase reporter assay, stable knockdown/overexpression clones, MTT proliferation assay, transwell migration assay |
PloS one |
Medium |
23383267
|
| 2020 |
The transcription factor ZNF582 directly regulates transcription of NRXN3 (and Nectin-3). Hypermethylation of the ZNF582 promoter reduces ZNF582 expression, leading to downregulation of NRXN3. Restoration of NRXN3 reverses the pro-metastatic effect of ZNF582 loss in nasopharyngeal carcinoma. |
ChIP-seq, ChIP-qPCR, luciferase reporter assay, bisulfite pyrosequencing, in vitro migration/invasion assays, in vivo metastasis models, rescue experiments |
Cancer communications (London, England) |
Medium |
33038291
|
| 2008 |
Nrxn3beta mRNA expression is upregulated in the globus pallidus of mice developing short-term cocaine appetence, implicating NRXN3 adhesion molecules in synaptic plasticity of basal ganglia neurons involved in indirect pathways of reward-related learning. |
mRNA quantification in dissected brain regions after cocaine exposure in mice |
Neuroreport |
Low |
18418251
|
| 2025 |
NRXN3 competitively blocks caspase-3 binding to RSK1, thereby inhibiting RSK1-dependent phosphorylation of caspase-3 at T152. Inhibition of this phosphorylation impairs caspase-3 interaction with the ubiquitin ligase component FBXO1, enhancing caspase-3 stability and facilitating caspase-3/GSDME-dependent pyroptotic cell death and chemosensitivity in intrahepatic cholangiocarcinoma. |
Genome-scale CRISPR-Cas9 screen, RNA-seq, immunoprecipitation-mass spectrometry (IP-MS), in vitro and in vivo functional experiments |
Journal of advanced research |
Medium |
40324630
|
| 2025 |
NRXN3 forms a complex with its ligand neuroligin 1 (NLGN1) in the hippocampus. Downregulation of both NRXN3 and NLGN1 precedes synaptic plasticity alterations (reduced dendritic branch and spine lengths) and depression-related behaviors induced by maternal separation stress in rats, suggesting the NRXN3-NLGN1 complex mediates synaptic plasticity changes underlying stress-induced depression susceptibility. |
Rat maternal separation model, Western blot, behavioral assays, hippocampal morphological analysis (branch and spine quantification) |
Brain research |
Low |
40286836
|
| 2025 |
Knockdown of Nrxn3 in the central amygdala of rats significantly increased the nociceptive pain response to inflammatory orofacial pain (myofascial pain model) and increased c-Fos levels in the central amygdala, lateral parabrachial nucleus, trigeminal ganglia, and trigeminal nucleus caudalis, indicating that Nrxn3 expression in the central amygdala attenuates nociceptive orofacial pain by reducing neuronal activity in the orofacial pain pathway. |
shRNA knockdown (stereotaxic infusion), von Frey filament testing, c-Fos immunostaining, meal duration measurement |
Neurobiology of pain (Cambridge, Mass.) |
Medium |
41466820
|
| 2023 |
A circular RNA originating from the Nrxn3 locus (circNrxn3) binds the splicing factor SAM68 (RNA immunoprecipitation), and its knockdown alters splicing of Nrxn3 mRNA and expression of genes in learning/memory pathways, enhancing sucrose self-administration and motivation for reward in the orbitofrontal cortex. |
RNA immunoprecipitation, RNA sequencing, qPCR, in vivo shRNA knockdown, sucrose self-administration behavioral assay |
Progress in neurobiology |
Low |
38036039
|
| 2023 |
Loss-of-function variants in NRXN3 (including homozygous and compound heterozygous missense/splice-site mutations validated by CRISPR-edited cell functional studies) cause a novel autosomal recessive neurodevelopmental syndrome with developmental delay, movement disorder, and behavioral problems, phenotypically consistent with homozygous Nrxn3α/β knockout mice. |
Whole exome sequencing, CRISPR-edited cell lines, in-silico analysis, phenotype-genotype correlation with mouse KO model |
Gene |
Medium |
36898513
|