Quantitative proteomics identifies a Dab2/integrin module regulating cell migration
| Autor: | Jonathan A. Cooper, Anjali Teckchandani, Julian D. Watts, Christine Henderson, Natalie Toida, Jake Goodchild, Bernd Wollscheid |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Proteomics
Integrins Endocytic cycle Integrin Integrin alpha1 Adaptor Protein Complex 2 Nerve Tissue Proteins Biology Endocytosis CD49c Bulk endocytosis Article Collagen receptor 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Animals Humans Research Articles 030304 developmental biology Adaptor Proteins Signal Transducing 0303 health sciences Integrin beta1 Tumor Suppressor Proteins Cell Membrane Membrane Proteins Cell Biology Vinculin Clathrin Cell biology Protein Transport 030220 oncology & carcinogenesis biology.protein Integrin beta 6 Apoptosis Regulatory Proteins HeLa Cells |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | 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 beta1, alpha1, alpha2, and alpha3 but not alpha5 or alphav chains were specifically increased on Dab2-deficient HeLa cells. Dab2 colocalizes with integrin beta1 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 beta1 and vinculin to the leading edge. By manipulating intracellular and surface integrin beta1 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. |
| Databáze: | OpenAIRE |
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