Quantitative proteomics identifies a Dab2/integrin module regulating cell migration

Clathrin-associated endocytic adapters recruit cargoes to coated pits as a first step in endocytosis. We developed an unbiased quantitative proteomics approach to identify and quantify glycoprotein cargoes for an endocytic adapter, Dab2. Surface levels of integrins beta 1, alpha 1, alpha 2, and beta 3 but not alpha 5 or alpha v chains were specifically increased on Dab2-deficient HeLa cells. Dab2 colocalizes with integrin beta 1 in coated pits that are dispersed over the cell surface, suggesting that it regulates bulk endocytosis of inactive integrins. Depletion of Dab2 inhibits cell migration and polarized movement of integrin beta 1 and vinculin to the leading edge. By manipulating intracellular and surface integrin beta 1 levels, we show that migration speed correlates with the intracellular integrin pool but not the surface level. Together, these results suggest that Dab2 internalizes integrins freely diffusing on the cell surface and that Dab2 regulates migration, perhaps by maintaining an internal pool of integrins that can be recycled to create new adhesions at the leading edge.