Circular dorsal ruffles are dynamic actin-based structures on the plasma membrane. They form in response to growth factor stimulation, which induces activation of the Src kinase and the transient rearrangement of the actin cytoskeleton. In their study on page , Reinhard Fässler and colleagues now discover that signalling crosstalk between the epidermal growth factor (EGF) receptor and integrins is required to mediate dorsal ruffle formation. The researchers show that integrin-α5β1-mediated adhesion to fibronectin and integrin-linked kinase (ILK) are required for EGF-induced ruffling in fibroblasts. Furthermore, they find that the localisation of active Src to focal adhesions is impaired in ILK−/− cells stimulated with EGF, suggesting that ILK regulates ruffle formation by controlling Src activity at adhesions. SILAC-based mass spectrometry and siRNA-mediated protein knockdown experiments reveal the tumour suppressor cylindromatosis (CYLD) as a target protein for integrin–ILK and EGFR signal crosstalk. Tyrosine phosphorylation of CYLD in response to EGF stimulation requires the presence of ILK and Src and is necessary for dorsal ruffling. These data thus highlight how the interplay between growth factor receptor and integrin signalling mediates fast actin cytoskeletal rearrangements during circular dorsal ruffle formation.
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