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Mechanotransduction In Vivo by Repeated Talin Stretch-Relaxation Events Depends upon Vinculin

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posted on 30.06.2015, 11:43 by N. Bate, F. Margadant, L. L. Chew, X. Hu, H. Yu, X. Zhang, M. Sheetz
Mechanotransduction is a critical function for cells, in terms of cell viability, shaping of tissues, and cellular behavior. In vitro, cellular level forces can stretch adhesion proteins that link extracellular matrix to the actin cytoskeleton exposing hidden binding sites. However, there is no evidence that in vivo forces produce significant in vivo stretching to cause domain unfolding. We now report that the adhesion protein, talin, is repeatedly stretched by 100–350 nm in vivo by myosin contraction of actin filaments. Using a functional EGFP-N-Talin1-C-mCherry to measure the length of single talin molecules, we observed that the C-terminal mCherry was normally displaced in the direction of actin flow by 90 to >250 nm from N-EGFP but only by 50–60 nm (talin's length in vitro) after myosin inhibition. Individual talin molecules transiently stretched and relaxed. Peripheral, multimolecular adhesions had green outside and red proximal edges. They also exhibited transient, myosin-dependent stretching of 50–350 nm for 6–16 s; however, expression of the talin-binding head of vinculin increased stretching to about 400 nm and suppressed dynamics. We suggest that rearward moving actin filaments bind, stretch, and release talin in multiple, stochastic stick-slip cycles and that multiple vinculin binding and release cycles integrate pulling on matrices into biochemical signals.

History

Citation

PLoS Biology, 2011, 9(12), e1001223

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Biochemistry

Version

VoR (Version of Record)

Published in

PLoS Biology

Publisher

Public Library of Science

issn

1544-9173

eissn

1545-7885

Copyright date

2011

Available date

30/06/2015

Publisher version

http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001223

Language

en