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Research Database PMU-SQQUID

Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts.
Thompson, O; Kleino, I; Crimaldi, L; Gimona, M; Saksela, K; Winder, SJ;
PLoS One. 2008; 3(11):e3638
Originalarbeiten (Zeitschrift)

PMU-Authors

Gimona Mario

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.


Useful keywords (using NLM MeSH Indexing)

Actins/metabolism

Animals

Biological Markers/metabolism

Cell Adhesion/physiology*

Cell Surface Extensions/metabolism*

Cell Surface Extensions/ultrastructure

Cells, Cultured

Cortactin/metabolism

Dystroglycans/genetics

Dystroglycans/metabolism*

Humans

Mice

Myoblasts/cytology*

Myoblasts/physiology

Phosphoproteins/genetics

Phosphoproteins/metabolism*

Recombinant Fusion Proteins/genetics

Recombinant Fusion Proteins/metabolism

src Homology Domains

src-Family Kinases/antagonists*

inhibitors

src-Family Kinases/genetics

src-Family Kinases/metabolism*