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Recruitment of Dbl by Ezrin and Dystroglycan Drives Membrane Proximal Cdc42 Activation and Filopodia Formation
Clare L. Batchelor, Jen R. Higginson, Yun-Ju Chen, Cristina Vanni, Alessandra Eva and Steve J. Winder
volume 6 | issue 3
1 February 2007Pages: 353 - 363
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Dystroglycan is an essential laminin binding cell adhesion molecule which is also an adaptor for several SH2 domain-containing signalling molecules and as a scaffold for the ERK-MAP kinase cascade. Loss of dystroglycan function is implicated in muscular dystrophies and the aetiology of epithelial cancers. We have previously demonstrated a role for dystroglycan and ezrin in the formation of filopodia structures. Here we demonstrate the existence of a dystroglycan:ezrin:Dbl complex that is targeted to the membrane by dystroglycan where it drives local Cdc42 activation and the formation of filopodial. Deletion of an ezrin binding site in dystroglycan prevented the association with ezrin and Dbl and the formation of filopodia. Furthermore, expression of the dystroglycan cytoplasmic domain alone had a dominant-negative effect on filopodia formation and Cdc42 activation by sequestering ezrin and Dbl away from the membrane. Depletion of dystroglycan inhibited Cdc42-induced filopodia formation. For the first time we also demonstrate co-localisation of Cdc42 and dystroglycan at the tips of dynamic filopodia.
Authors
Clare L. Batchelor
University of Sheffield, Sheffield, UK
Jen R. Higginson
University of Sheffield, Sheffield, UK
Yun-Ju Chen
University of Sheffield, Sheffield, UK
Cristina Vanni
Istituto G. Gaslini, Genova, Italy
Alessandra Eva
Istituto G. Gaslini, Genova, Italy
Steve J. Winder
University of Sheffield, Sheffield, UK
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.