Document Detail


Transient receptor potential canonical channel 1 impacts on mechanosignaling during cell migration.
MedLine Citation:
PMID:  23053481     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cell migration is crucial for many important physiological and pathophysiological processes ranging from embryogenesis to tumor metastasis. It requires the coordination of mechanical forces generated in different regions of the migrating cell. It has been proposed that stretch-activated, Ca(2+)-permeable channels are involved in mechanosignaling during cell migration. To date, the molecular identity of these channels is only poorly defined. Here, we investigated the contribution of TRPC1 channels to mechanosignaling during cell migration. We used primary cultures of synovial fibroblasts from TRPC1(-/-) mice and the wild-type littermates or Madin-Darby canine kidney (MDCK-F) cells with increased or decreased TRPC1 expression. TRPC1(-/-) fibroblasts have the same migratory phenotype as siTRPC1 MDCK-F cells, with a largely increased projected cell area and impaired directionality. Measurements of the intracellular Ca(2+) concentration ([Ca(2+)](i)) were combined with time-lapse video microscopic cell migration experiments. Cells were seeded on elastic silicone membranes. Uniaxial stretch elicits a graded elevation of the [Ca(2+)](i) in TRPC1-expressing cells. In contrast, TRPC1(-/-) fibroblasts or siTRPC1 MDCK-F cells do not react to 0.4 %, and the response to 4 % stretch is attenuated. Similarly, siTRPC1 MDCK-F cells do not alter their direction of migration upon mechanical stimulation, which contrasts the behavior of TRPC1-overexpressing cells which turn into the direction of stretch. Impaired mechanosignaling in siTRPC1 MDCK-F cells leads to accelerated lamellipodial protrusions. Finally, artificially decreasing membrane tension with the detergent deoxycholate impairs the migration of TRPC1-overexpressing cells, but not of siTRPC1 cells. Taken together, our findings indicate that TRPC1 channels are linked to mechanosignaling during cell migration.
Authors:
Anke Fabian; Jessica Bertrand; Otto Lindemann; Thomas Pap; Albrecht Schwab
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-11
Journal Detail:
Title:  Pflugers Archiv : European journal of physiology     Volume:  -     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute für Physiologie II, Westfälische Wilhelms-Universität, Robert-Koch-Str. 27b, 48149, Münster, Germany.
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