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ARTICLE |
Quantitative proteomics identifies a Dab2/integrin module regulating cell migration
Correspondence to Jonathan A. Cooper: jcooper{at}fhcrc.org
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 β1,
1, 2, and 3 but not 5 or v chains were specifically increased on Dab2-deficient HeLa cells. Dab2 colocalizes with integrin β1 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 β1 and vinculin to the leading edge. By manipulating intracellular and surface integrin β1 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.
C. Henderson's present address is Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006.
Abbreviations used in this paper: ARH, autosomal recessive hypercholesterolemia; CSC, cell surface capture; HFF, human foreskin fibroblast; LDLR, low density lipoprotein receptor; shRNA, short hairpin RNA; SILAC, stable isotope labeling with amino acids in cell culture; Tfn, transferrin; TfnR, Tfn receptor.
© 2009 Teckchandani et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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