Mechanotransduction in talin through the interaction of the R8 domain with DLC1
File(s)
Author(s)
Type
Journal Article
Abstract
The mechanical unfolding of proteins is a cellular mechanism for force transduction with potentially broad implications in cell fate. Despite this, the mechanism by which protein unfolding elicits differential downstream signalling pathways remains poorly understood. Here, we used protein engineering, atomic force microscopy, and biophysical tools to delineate how protein unfolding controls cell mechanics. Deleted in liver cancer 1 (DLC1) is a negative regulator of Ras homolog family member A (RhoA) and cell contractility that regulates cell behaviour when localised to focal adhesions bound to folded talin. Using a talin mutant resistant to force-induced unfolding of R8 domain, we show that talin unfolding determines DLC1 downstream signalling and, consequently, cell mechanics. We propose that this new mechanism of mechanotransduction may have implications for a wide variety of associated cellular processes.
Date Issued
2018-07-20
Date Acceptance
2018-06-19
Citation
PLoS Biology, 2018, 16 (7), pp.1-20
ISSN
1544-9173
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
20
Journal / Book Title
PLoS Biology
Volume
16
Issue
7
Copyright Statement
© 2018 Haining et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor
Commission of the European Communities
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000440397800020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
282051
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
FOCAL ADHESION KINASE
MOLECULAR-DYNAMICS
VINCULIN
CELL
PROTEIN
FORCE
INVASION
REVEALS
GROMACS
TENSION
Publication Status
Published
Article Number
e2005599
Date Publish Online
2018-07-20