| 2011 |
Cbln2 specifically binds to α and β isoforms of neurexin carrying the splice site 4 insert [NRXs(S4+)] and induces synaptogenesis in cerebellar, hippocampal and cortical neurons in vitro. This binding is insensitive to extracellular Ca2+ concentrations. |
In vitro synaptogenesis assay, binding assay, competition with neuroligin 1 |
The European journal of neuroscience |
High |
21410790
|
| 2007 |
Cbln2 is secreted as an N-linked glycoprotein and can form not only homomeric but also heteromeric complexes with other Cbln family members (Cbln1, Cbln3, Cbln4) in vitro; heteromer formation modulates trafficking and secretion. |
Mammalian heterologous cell expression, co-immunoprecipitation, secretion assays |
The European journal of neuroscience |
High |
17331201
|
| 2012 |
Cbln2 binds directly to the N-terminal domain of GluRδ1 (glutamate receptor δ1) and mediates preferentially inhibitory presynaptic differentiation of cultured cortical neurons via neurexins containing splice segment 4. Synaptogenic activity of Cbln2 is suppressed by the extracellular domain of NRXN1α or NRXN1β(S4+). |
HEK293T cell coculture synaptogenesis assay, direct binding assay, receptor-ligand competition |
Journal of neurochemistry |
High |
22191730
|
| 2011 |
Cbln2 shows robust binding to NRXN1α and β-NRXNs selectively for splice segment 4-containing variants, and induces presynaptic differentiation of cortical neurons; surface plasmon resonance reveals Cbln2 has lower affinity for neurexins than Cbln1. |
Surface plasmon resonance, synaptogenesis assay with cortical neurons, binding competition |
Biochemical and biophysical research communications |
High |
21356198
|
| 2012 |
Cbln2 binds to GluRδ2 and neurexins 1-3, similar to Cbln1. Ectopic expression of Cbln2 in Purkinje cells of Cbln1-null mice rescues cerebellar deficits, demonstrating functional redundancy mediated by shared receptor binding properties. |
Transgenic mouse rescue experiment, binding assay, Cbln2 knockout mouse generation |
Journal of neurochemistry |
High |
22117778
|
| 2018 |
GluD1 (δ1 glutamate receptor) requires Cbln2 to assemble and maintain hippocampal excitatory synapses; GluD1 synaptic actions are absent in Cbln2 knockout mice. The mechanism involves a tripartite complex: Cbln2 bridges postsynaptic GluD1 and presynaptic neurexin 1β carrying splice site 4 insert (+S4). |
Cbln2 knockout mouse electrophysiology, genetic epistasis, loss-of-function with defined synaptic phenotype |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29784783
|
| 2018 |
Cbln1/Cbln2 double knockout mice display a selective ~50% decrease in hippocampal synapse density in stratum lacunosum moleculare of CA1 and dentate gyrus in 6-month-old mice, and similar decreases in striatum and retrosplenial cortex, demonstrating that Cbln2 contributes to long-term synapse maintenance rather than initial formation. |
Constitutive single, double, and triple KO mice; quantitative synapse density analysis; behavioral testing |
The Journal of neuroscience |
High |
29691328
|
| 2022 |
At CA1→subiculum synapses, Cbln2 mediates neurexin-1(SS4+)-dependent enhancement of NMDA receptors and neurexin-3(SS4+)-dependent suppression of AMPA receptors via GluD1, without affecting synapse formation or spine numbers. In the prefrontal cortex, Nrxn1SS4+-Cbln2 signaling selectively controls NMDA receptors. |
Constitutive Cbln2 KO in mice, electrophysiology at defined synapses, circuit-specific analysis |
eLife |
High |
36205393
|
| 2021 |
Cbln2 KO mice display compulsive behaviors including stereotypic pattern running, marble burying, explosive jumping, and excessive nest building, accompanied by decreased brain serotonin levels. Conditional deletion of Cbln2 from dorsal raphe neurons or presynaptic neurons synapsing onto dorsal raphe neurons reproduced compulsive behaviors. Injection of recombinant Cbln2 protein into dorsal raphe reversed compulsive behaviors. |
Constitutive and conditional KO mice, recombinant protein injection, pharmacological rescue with 5-HTP and fluoxetine |
Molecular psychiatry |
High |
34158618
|
| 2021 |
Hominini-specific deletions containing SOX5-binding sites within a retinoic acid-responsive CBLN2 enhancer drive transient PFC-enriched, laminar-specific upregulation of CBLN2 during midfetal development. In situ genetic humanization of the mouse Cbln2 enhancer increases and ectopically expands laminar Cbln2 expression and promotes PFC dendritic spine formation. |
Comparative transcriptomics, enhancer humanization knock-in mouse, in situ hybridization, dendritic spine analysis |
Nature |
High |
34599306
|
| 2023 |
CBLN2 promotes endothelial-mesenchymal transition (EndMT) in pulmonary hypertension by activating the NF-κB/HIF-1α/Twist1 pathway; CBLN2 siRNA, NF-κB inhibitor PDTC, or HIF-1α inhibitor KC7F2 each inhibited hypoxia-induced EndMT. |
Hypoxia-induced rat PH model, siRNA knockdown, pharmacological inhibition, endothelial/mesenchymal marker immunostaining |
Life sciences |
Medium |
37355224
|
| 2024 |
A GRID1 variant at the Cbln2/Cbln4 interaction site in the distal amino terminal domain disrupts complex formation between GluD1 and Cbln2, demonstrating that this domain mediates the GluD1-Cbln2 interaction required for synapse organization. |
Biochemical co-immunoprecipitation, mutagenesis of human GRID1 variant, electrophysiology |
Human molecular genetics |
Medium |
37944084
|
| 2023 |
Retinoic acid supplementation increases RARα binding to Cbln2 promoters (confirmed by ChIP assay), upregulates CBLN2 expression in cerebellum, and ameliorates motor incoordination in VPA-induced autism rat model, establishing an RARα-CBLN2 regulatory axis. |
ChIP assay for RARα binding to Cbln2 promoter, retinoic acid supplementation, motor behavior testing, Purkinje cell morphology |
Neuroscience letters |
Medium |
37247722
|
| 2025 |
SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription following spinal nerve ligation (SNL). siRNA knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. Exogenous CBLN2 activates NF-κB signaling and increases proinflammatory cytokines and neuronal hyperexcitability. |
ChIP for SOX11 binding, siRNA knockdown, intrathecal injection of recombinant CBLN2, electrophysiology, high-throughput sequencing |
Neuroscience bulletin |
Medium |
41162740
|
| 2025 |
TET3-mediated demethylation of the Cbln2 promoter drives upregulation of CBLN2 in trigeminal ganglion neurons following partial infraorbital nerve transection. Exogenous CBLN2 potentiates neuronal excitability and activates ERK signaling; MEK inhibition abolished CBLN2-induced hypersensitivity and suppressed proinflammatory cytokines. |
Methylation-specific PCR, bisulfite sequencing, Tet3 siRNA knockdown, patch-clamp electrophysiology, pharmacological MEK inhibition |
The journal of headache and pain |
Medium |
40665237
|
| 2018 |
Novel peptides derived from CBLN2 precursor protein are identified in mouse spinal cord dorsal horn by mass spectrometry, and intrathecal injection of two of three CBLN2-derived peptides induced mechanical hypersensitivity in mice. |
Mass spectrometry, intrathecal injection, von Frey testing |
Neuropeptides |
Medium |
29705514
|
| 2024 |
CBLN2 overexpression inhibits STAT3-induced PD-L1 and beta-catenin activation in colorectal cancer cells, suppresses oncogenic cell properties in vitro and tumor growth in vivo, and improves immune checkpoint blockade efficiency. |
Overexpression in CRC cell lines, in vivo tumor model, immunological assays |
International immunopharmacology |
Low |
39577217
|
| 2017 |
Using knockin reporter mice for Cbln2, Cbln2 is expressed in specific subsets of neurons (not all neurons): broadly in largely non-overlapping subpopulations of excitatory cortical neurons, selectively in inhibitory interneurons of the olfactory bulb, and at extremely high levels in the nucleus of the lateral olfactory tract. |
Knockin reporter mice, in situ hybridization, immunofluorescence |
The Journal of comparative neurology |
Medium |
28714144
|