Document Detail


CRMP-2 Is Involved in Axon Growth Inhibition Induced by RGMa In Vitro and In Vivo.
MedLine Citation:
PMID:  23275173     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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-3β, in vitro by culturing neonatal rat primary cortical neurons with RGMa protein, Rho-kinase inhibitor (Y-27632), and GSK-3β 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-3β 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-3β signaling pathways.
Authors:
Tianzhu Wang; Xiaohui Wu; Cheng Yin; Damon Klebe; John H Zhang; Xinyue Qin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-30
Journal Detail:
Title:  Molecular neurobiology     Volume:  -     ISSN:  1559-1182     ISO Abbreviation:  Mol. Neurobiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900963     Medline TA:  Mol Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
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