UNC5C

更新于：2025-05-07

基本信息

别名

Netrin receptor UNC5C、Protein unc-5 homolog 3、Protein unc-5 homolog C

+ [3]

简介

Receptor for netrin required for axon guidance (By similarity). Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (By similarity). NTN1/Netrin-1 binding might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Axon repulsion in growth cones may also be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Might also collaborate with DSCAM in NTN1-mediated axon repulsion independently of DCC (By similarity). Also involved in corticospinal tract axon guidance independently of DCC (By similarity). Involved in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity).

关联

100 项与 UNC5C 相关的临床结果

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100 项与 UNC5C 相关的转化医学

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0 项与 UNC5C 相关的专利（医药）

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170

项与 UNC5C 相关的文献（医药）

2025-05-01·eBioMedicine

Multi-ancestry genome-wide association meta-analysis identifies novel associations and informs genetic risk prediction for Hirschsprung disease

Article

作者: Song, You-Qiang ; Ceccherini, Isabella ; Zhang, Detao ; Xiong, Zewei ; Cheah, Kathryn Song-Eng ; Tam, Paul Kwong-Hang ; Borrego, Salud ; Pakarinen, Mikko P ; So, Man-Ting ; Wang, Yanbing ; Tang, Clara Sze-Man ; Feenstra, Bjarke ; Zhong, Yuanxin ; Ma, Zuyi ; Lui, Vincent Chi-Hang ; Alves, Maria M ; Fadista, João ; Garcia-Barcelo, Maria-Merce ; Sham, Pak Chung

BACKGROUNDHirschsprung disease (HSCR) is a rare, congenital disease characterized by the absence of enteric ganglia in the hindgut. Common genetic variation contributes substantially to the heritability of the disease yet only three HSCR-associated loci were identified from genome-wide association studies (GWAS) thus far.METHODSWe performed the largest multi-ancestry meta-analysis of GWAS to date, totalling 1250 HSCR cases and 7140 controls. Prioritized candidate genes were further characterized using single-cell transcriptomic data of developing human and mouse gut for their roles in development of enteric nervous system (ENS). Functional characterisation using human cells and zebrafish models was performed. Global and ancestry-matched polygenic risk score (PRS) models were derived and evaluated for predicting risk of HSCR.FINDINGSWe identified four HSCR-susceptibility loci, with three loci (JAG1, HAND2 and ZNF25) reaching genome-wide significance and one putative locus (UNC5C) prioritized by functional relevance. Spatiotemporal analysis revealed hotspots of gene dysregulation during ENS development. Functional analyses further demonstrated that knockdown of the candidate genes impaired cell migration and zebrafish knockouts displayed abnormal ENS development. We also demonstrated comparable performance for a PRS model derived from multi-ancestry meta-analysis to those of ancestry-matched PRS models, supporting its potential clinical application in risk prediction of HSCR across populations.INTERPRETATIONOverall, the meta-analysis implicated novel genes, pathways and spatiotemporal developmental hotspots in the genetic aetiology of HSCR. Development of a PRS universally applicable irrespective of ancestries may leverage its clinical utility in risk prediction.FUNDINGThe full list of funding bodies can be found in the Acknowledgements section.

2025-03-01·Neurotherapeutics

Delayed atorvastatin delivery promotes recovery after experimental spinal cord injury

Article

作者: Langley, Monica R ; Buchl, Samuel C ; Hur, Benjamin ; Simon, Whitney L ; Scarisbrick, Isobel A ; Sung, Jaeyun ; Kim, Ha Neui

Spinal cord injury (SCI) significantly alters gene expression, potentially impeding functional recovery. This study investigated the effects of atorvastatin, a widely prescribed cholesterol-lowering drug, on gene expression and functional recovery in a chronic murine SCI model. Female C57BL/6J mice underwent moderate 0.25 mm lateral compression SCI and received daily atorvastatin (10 mg/kg) or vehicle-only injections from two weeks post-injury for four weeks. Sensorimotor functions were assessed using the Basso Mouse Scale (BMS), its subscore, and the inclined plane test. RNA sequencing of spinal cord tissues identified robust transcriptomic changes from SCI and a smaller subset from atorvastatin treatment. Atorvastatin enhanced sensorimotor recovery within two weeks of treatment initiation, with effects persisting to the experimental endpoint. Pathway analysis showed atorvastatin enriched neural regeneration processes including Fatty Acid Transport, Axon Guidance, and the Endocannabinoid Developing Neuron Pathway; improved mitochondrial function via increased TCA Cycle II and reduced Mitochondrial Dysfunction; and decreased Inhibition of Matrix Metalloproteases. Key gene drivers included Fabp7, Unc5c, Rest, and Klf4. Together, these results indicate atorvastatin's potential in chronic SCI recovery, especially where already indicated for cardiovascular protection.

2025-01-01·Journal of Neurochemistry

TRIM9 Controls Growth Cone Responses to Netrin Through DCC and UNC5C

Article

作者: Frasineanu, Anca G. ; Mutalik, Sampada P. ; Gupton, Stephanie L. ; Ho, Chris T. ; O'Shaughnessy, Ellen C. ; Shah, Aneri B.

ABSTRACTThe guidance cue netrin‐1 promotes both growth cone attraction and growth cone repulsion. How netrin‐1 elicits diverse axonal responses, beyond engaging the netrin receptor DCC and UNC5 family members, remains elusive. Here, we demonstrate that murine netrin‐1 induces biphasic axonal responses in cortical neurons: Attraction at lower concentrations and repulsion at higher concentrations using both a microfluidic‐based netrin‐1 gradient and bath application of netrin‐1. We find that repulsive turning in a netrin gradient is blocked by knockdown of UNC5C, whereas attractive turning is impaired by knockdown of DCC. TRIM9 is a brain‐enriched E3 ubiquitin ligase previously shown to bind and cluster the attractive receptor DCC at the plasma membrane and regulate netrin‐dependent attractive responses. However, whether TRIM9 also regulated repulsive responses to netrin‐1 remained to be seen. In this study, we show that TRIM9 localizes and interacts with both the attractive netrin receptor DCC and the repulsive netrin receptor, UNC5C. We find that deletion of murine Trim9 alters both attractive and repulsive axon turning and changes in growth cones size in response to murine netrin‐1. TRIM9 was required for netrin‐1‐dependent changes in the surface levels of DCC and UNC5C in the growth cone during morphogenesis. We demonstrate that DCC at the membrane regulates the growth cone area and show that TRIM9 negatively regulates FAK activity in the absence of both repulsive and attractive concentrations of netrin‐1. Together, our work demonstrates that TRIM9 interacts with and regulates both DCC and UNC5C during attractive and repulsive axonal responses to netrin‐1.

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