Document Detail


Mechanosensitive TRPC1 Channels Promote Calpain Proteolysis of Talin to Regulate Spinal Axon Outgrowth.
MedLine Citation:
PMID:  23283340     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Intracellular Ca(2+) signals control the development and regeneration of spinal axons downstream of chemical guidance cues, but little is known about the roles of mechanical cues in axon guidance. Here we show that transient receptor potential canonical 1 (TRPC1) subunits assemble mechanosensitive (MS) channels on Xenopus neuronal growth cones that regulate the extension and direction of axon outgrowth on rigid, but not compliant, substrata. Reducing expression of TRPC1 by antisense morpholinos inhibits the effects of MS channel blockers on axon outgrowth and local Ca(2+) transients. Ca(2+) influx through MS TRPC1 activates the protease calpain, which cleaves the integrin adaptor protein talin to reduce Src-dependent axon outgrowth, likely through altered adhesion turnover. We found that talin accumulates at the tips of dynamic filopodia, which is lost upon cleavage of talin by active calpain. This pathway may also be important in axon guidance decisions since asymmetric inhibition of MS TRPC1 is sufficient to induce growth cone turning. Together our results suggest that Ca(2+) influx through MS TRPC1 on filopodia activates calpain to control growth cone turning during development.
Authors:
Patrick C Kerstein; Bridget T Jacques-Fricke; Juliana Rengifo; Brian J Mogen; Justin C Williams; Philip A Gottlieb; Fredrick Sachs; Timothy M Gomez
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  273-85     Citation Subset:  IM    
Affiliation:
Department of Neuroscience and Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, Department of Biology, Universidad ICESI, 122-135 Pance, Cali, Colombia, Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin 53706, and Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214.
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