Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity

Kumar, A., Ouyang, M., Van den Dries, K., McGhee, E. J., Tanaka, K., Anderson, M. D., Groisman, A., Goult, B. T., Anderson, K. I. and Schwartz, M. A. (2016) Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity. Journal of Cell Biology, 213(3), pp. 371-383. (doi: 10.1083/jcb.201510012) (PMID:27161398) (PMCID:PMC4862330)

Abstract

Integrin-dependent adhesions are mechanosensitive structures in which talin mediates a linkage to actin filaments either directly or indirectly by recruiting vinculin. Here, we report the development and validation of a talin tension sensor. We find that talin in focal adhesions is under tension, which is higher in peripheral than central adhesions. Tension on talin is increased by vinculin and depends mainly on actin-binding site 2 (ABS2) within the middle of the rod domain, rather than ABS3 at the far C terminus. Unlike vinculin, talin is under lower tension on soft substrates. The difference between central and peripheral adhesions requires ABS3 but not vinculin or ABS2. However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3. These results indicate that central versus peripheral adhesions must be organized and regulated differently, and that ABS2 and ABS3 have distinct functions in spatial variations and stiffness sensing. Overall, these results shed new light on talin function and constrain models for cellular mechanosensing.

• Item Type: Articles
• Additional Information: This work was supported by a U.S. Public Health Service grant (PO1 GM98412) to M.A. Schwartz. E.J. McGhee and K.I. Anderson were on June 16, 2016 jcb.rupress.org Downloaded from Published May 9, 2016 382 JCB • Volume 213 • Number 3 • 2016 supported by Cancer Research UK with a core grant fund. K. Tanaka was supported by Japan Society for the Promotion of Science postdoctoral fellowships for abroad research.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Anderson, Professor Kurt and McGhee, Dr Ewan
• Authors: Kumar, A., Ouyang, M., Van den Dries, K., McGhee, E. J., Tanaka, K., Anderson, M. D., Groisman, A., Goult, B. T., Anderson, K. I., and Schwartz, M. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Cell Biology
• Publisher: Rockefeller University Press
• ISSN: 0021-9525
• ISSN (Online): 1540-8140
• Published Online: 09 May 2016
• Copyright Holders: Copyright © 2016 Kumar et al.
• First Published: First published in Journal of Cell Biology 213(3):371-383
• Publisher Policy: Reproduced under a Creative Commons License