Enigma proteins regulate YAP mechanotransduction

Elbediwy, Ahmed, Vanyai, Hannah, Diaz-de-la-Loza, Maria-del-Carmen, Frith, David, Snijders, Ambrosius P. and Thompson, Barry J. (2018) Enigma proteins regulate YAP mechanotransduction. Journal of Cell Science, 131(22), jcs22178. ISSN (print) 0021-9533

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Abstract

Human cells can sense mechanical stress acting upon integrin adhesions and respond by sending the YAP (also known as YAP1) and TAZ (also known as WWTR1) transcriptional co-activators to the nucleus to drive TEAD-dependent transcription of target genes. How integrin signaling activates YAP remains unclear. Here, we show that integrin-mediated mechanotransduction requires the Enigma and Enigma-like proteins (PDLIM7 and PDLIM5, respectively; denoted for the family of PDZ and LIM domain-containing proteins). YAP binds to PDLIM5 and PDLIM7 (hereafter PDLIM5/7) via its C-terminal PDZ-binding motif (PBM), which is essential for full nuclear localization and activity of YAP. Accordingly, silencing of PDLIM5/7 expression reduces YAP nuclear localization, tyrosine phosphorylation and transcriptional activity. The PDLIM5/7 proteins are recruited from the cytoplasm to integrin adhesions and F-actin stress fibers in response to force by binding directly to the key stress fiber component α-actinin. Thus, forces acting on integrins recruit Enigma family proteins to trigger YAP activation during mechanotransduction.This article has an associated First Person interview with the first author of the paper.

Item Type: Article
Additional Information: This work was supported by the Francis Crick Institute and the Wellcome Trust [award number: 102853/B/13/Z].
Research Area: Biological sciences
Cancer studies
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing
Faculty of Science, Engineering and Computing > School of Life Sciences, Pharmacy and Chemistry
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Depositing User: Ahmed Elbediwy
Date Deposited: 13 Feb 2019 13:59
Last Modified: 13 Mar 2019 09:06
DOI: https://doi.org/10.1242/jcs.221788
URI: http://eprints.kingston.ac.uk/id/eprint/42592

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