Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/12717
Title: Talin contains a C-terminal calpain2 cleavage site important in focal adhesion dynamics.
Authors: Bate, N.
Gingras, A. R.
Bachir, A.
Horwitz, R.
Ye, F.
Patel, B.
Goult, B. T.
Critchley, D. R.
First Published: 4-Apr-2012
Publisher: Public Library of Science
Citation: PLOS ONE, 2012, 7 (4), pp. e34461-e34461
Abstract: Talin is a large (∼2540 residues) dimeric adaptor protein that associates with the integrin family of cell adhesion molecules in cell-extracellular matrix junctions (focal adhesions; FAs), where it both activates integrins and couples them to the actin cytoskeleton. Calpain2-mediated cleavage of talin between the head and rod domains has previously been shown to be important in FA turnover. Here we identify an additional calpain2-cleavage site that removes the dimerisation domain from the C-terminus of the talin rod, and show that an E2492G mutation inhibits calpain cleavage at this site in vitro, and increases the steady state levels of talin1 in vivo. Expression of a GFP-tagged talin1 E2492G mutant in CHO.K1 cells inhibited FA turnover and the persistence of cell protrusion just as effectively as a L432G mutation that inhibits calpain cleavage between the talin head and rod domains. Moreover, incorporation of both mutations into a single talin molecule had an additive effect clearly demonstrating that calpain cleavage at both the N- and C-terminal regions of talin contribute to the regulation of FA dynamics. However, the N-terminal site was more sensitive to calpain cleavage suggesting that lower levels of calpain are required to liberate the talin head and rod fragments than are needed to clip off the C-terminal dimerisation domain. The talin head and rod liberated by calpain2 cleavage have recently been shown to play roles in an integrin activation cycle important in FA turnover and in FAK-dependent cell cycle progression respectively. The half-life of the talin head is tightly regulated by ubiquitination and we suggest that removal of the C-terminal dimerisation domain from the talin rod may provide a mechanism both for terminating the signalling function of the talin rod and indeed for inactivating full-length talin thereby promoting FA turnover at the rear of the cell.
DOI Link: 10.1371/journal.pone.0034461
eISSN: 1932-6203
Links: http://hdl.handle.net/2381/12717
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034461
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2012 Bate et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Biochemistry

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