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Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts

Thompson, O., Kleino, L., Crimaldi, L., Gimona, M., Saksela, K. and Winder, S.J. (2008) Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts. Plos One, 3 (11). Art No.e3638. ISSN 1932-6203

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Abstract

Background: Dystroglycan is a ubiquitously expressed cell adhesion receptor best understood in its role as part of the dystrophin glycoprotein complex of mature skeletal muscle. Less is known of the role of dystroglycan in more fundamental aspects of cell adhesion in other cell types, nor of its role in myoblast cell adhesion.

Principal Findings: We have examined the role of dystroglycan in the early stages of myoblast adhesion and spreading and found that dystroglycan initially associates with other adhesion proteins in large puncta morphologically similar to podosomes. Using a human SH3 domain phage display library we identified Tks5, a key regulator of podosomes, as interacting with beta-dystroglycan. We verified the interaction by immunoprecipitation, GST-pulldown and immunfluorescence localisation. Both proteins localise to puncta during early phases of spreading, but importantly following stimulation with phorbol ester, also localise to structures indistinguishable from podosomes. Dystroglycan overexpression inhibited podosome formation by sequestering Tks5 and Src. Mutation of dystroglycan tyrosine 890, previously identified as a Src substrate, restored podosome formation.

Conclusions: We propose therefore, that Src-dependent phosphorylation of beta-dystroglycan results in the formation of a Src/dystroglycan complex that drives the SH3-mediated association between dystroglycan and Tks5 which together regulate podosome formation in myoblasts.

Item Type: Article
Copyright, Publisher and Additional Information: © 2008 Thompson 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.
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > School of Biological Sciences (Sheffield) > Department of Biomedical Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 19 Jan 2010 11:31
Last Modified: 08 Feb 2013 16:59
Published Version: http://dx.doi.org/10.1371/journal.pone.0003638
Status: Published
Publisher: Public Library Science
Refereed: Yes
Identification Number: 10.1371/journal.pone.0003638
URI: http://eprints.whiterose.ac.uk/id/eprint/10306

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