RGD Reference Report - CRMP-2 is involved in axon growth inhibition induced by RGMa in vitro and in vivo. - Rat Genome Database
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CRMP-2 is involved in axon growth inhibition induced by RGMa in vitro and in vivo.

Authors: Wang, T  Wu, X  Yin, C  Klebe, D  Zhang, JH  Qin, X 
Citation: Wang T, etal., Mol Neurobiol. 2013 Jun;47(3):903-13. doi: 10.1007/s12035-012-8385-3. Epub 2012 Dec 30.
RGD ID: 9850122
Pubmed: (View Article at PubMed) PMID:23275173
DOI: Full-text: DOI:10.1007/s12035-012-8385-3

Repulsive guidance molecule-a (RGMa) is associated with axon growth inhibition in different central nervous system (CNS) injuries, but its signaling pathways remain unclear. We examined the involvement of collapsin response mediator protein-2 (CRMP-2), a common downstream target of Rho-kinase and GSK-3beta, in vitro by culturing neonatal rat primary cortical neurons with RGMa protein, Rho-kinase inhibitor (Y-27632), and GSK-3beta inhibitor. We examined CRMP-2 in vivo by suppressing RGMa expression using recombinant adenovirus (rAd-shRGMa) in a rat MCAO/reperfusion model. RGMa induced neurite retraction and CRMP-2 phosphorylation in vitro, which were reversed by either Rho-kinase or GSK-3beta inhibitors. After MCAO/reperfusion in rats, pCRMP-2 protein was greatly increased in the ischemic cortex, axons were damaged severely, Neurofilament-200 (NF-200) expression was significantly decreased, and neurological deficits were significant, which were all improved by down-regulating RGMa. We concluded RGMa inhibits axon growth by phosphorylating CRMP-2 via both Rho-kinase and GSK-3beta signaling pathways.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Rgma  (repulsive guidance molecule BMP co-receptor a)

Genes (Mus musculus)
Rgma  (repulsive guidance molecule family member A)

Genes (Homo sapiens)
RGMA  (repulsive guidance molecule BMP co-receptor a)


Additional Information