Non-amoeboid cell migration involves a cell extending a lamellipodium, which is then stabilised by integrin-containing focal adhesions (FAs). It is largely known how FAs are formed but less is known about how they are disassembled. Here (p. 863), Laura di Blasio and colleagues investigate the role of the kinase PDK1 is this process. The authors showed that PDK1 modulated the adhesion of endothelial cells on vitronectin. It did this by stimulating endocytosis of integrin αvβ3, which promotes the turnover of integrin-αvβ3-containing FAs. Further work showed that PDK1 dynamically localised to FAs just before their disassembly. It could also directly bind to and phosphorylate a threonine residue in the β3-integrin tail, and the authors found that this phosphorylation was responsible for regulating the integrin endocytosis. The PDK1-stimulated endocytosis required PI3K but did not require downstream activation of Akt. The authors conclude that PI3K promotes the membrane translocation of PDK1, which is mediated by its binding, through its PH domain, to PI3K-produced phosphoinositides. Finally, the authors showed that PDK1 silencing stabilises FAs in membrane protrusions, decreasing the migration of endothelial cells on vitronectin. High expression of αvβ3 integrin is a characteristic of angiogenic endothelium, and hence the results of the study suggest that PDK1 directly affects angiogenesis.

© 2015. Published by The Company of Biologists Ltd
2015