Document Detail


Mechanosensitive TRPC1 channels promote calpain proteolysis of talin to regulate spinal axon outgrowth.
MedLine Citation:
PMID:  23283340     Owner:  NLM     Status:  MEDLINE    
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
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:  2013-03-12     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  273-85     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Axons / metabolism*
Calcium / metabolism
Calcium Signaling / physiology
Calpain / metabolism*
Female
Growth Cones / metabolism*
Male
Neurons / cytology,  metabolism
Proteolysis
Pseudopodia / metabolism
Spinal Cord / cytology,  metabolism
TRPC Cation Channels / genetics,  metabolism*
Talin / metabolism*
Xenopus
Xenopus Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
F31 NS053076/NS/NINDS NIH HHS; F31 NS074732/NS/NINDS NIH HHS; F31NS053076/NS/NINDS NIH HHS; NS41564/NS/NINDS NIH HHS; R01 NS041564/NS/NINDS NIH HHS; T32 GM007507/GM/NIGMS NIH HHS; T32GM007507/GM/NIGMS NIH HHS; UL1 TR000427/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/TRPC Cation Channels; 0/TRPC1 protein, Xenopus; 0/Talin; 0/Xenopus Proteins; EC 3.4.22.-/Calpain; SY7Q814VUP/Calcium
Comments/Corrections

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