The Arf6 GEF GEP100/BRAG2 Regulates Cell Adhesion by Controlling Endocytosis of β1 Integrins
| Autor: | Kim Ly, James E. Casanova, Troy K. R. Lasell, Paul Melançon, Jillian L. Dunphy, Radim Moravec |
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| Rok vydání: | 2006 |
| Předmět: |
media_common.quotation_subject
Immunoblotting Integrin GTPase Biology Endocytosis Article General Biochemistry Genetics and Molecular Biology Cell Adhesion Guanine Nucleotide Exchange Factors Humans Immunoprecipitation Protein Isoforms Small GTPase RNA Small Interfering CELBIO Cell adhesion Internalization DNA Primers media_common Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) ADP-Ribosylation Factors Integrin beta1 Flow Cytometry Cell biology Protein Transport Microscopy Fluorescence SIGNALING ADP-Ribosylation Factor 6 biology.protein RNA Interference Guanine nucleotide exchange factor General Agricultural and Biological Sciences Intracellular HeLa Cells |
| Zdroj: | Current Biology. 16:315-320 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/j.cub.2005.12.032 |
| Popis: | SummaryThe small GTPase Arf6 has been shown to regulate the post-endocytic trafficking of a subset of membrane proteins, including β1 integrins, and inhibition of Arf6 function impairs both cell adhesion and motility [1]. The activity of Arf GTPases is regulated by a large family of guanine nucleotide exchange factors (GEFs) [2]. Arf-GEP100/BRAG2 is a GEF with reported specificity for Arf6 in vitro [3], but it is otherwise poorly characterized. Here we report that BRAG2 exists in two ubiquitously expressed isoforms, which we call BRAG2a and BRAG2b, both of which can activate Arf6 in vivo. Depletion of endogenous BRAG2 by siRNA leads to dramatic effects in the cell periphery; one such effect is an accumulation of β1 integrin on the cell surface and a corresponding enhancement of cell attachment and spreading on fibronectin-coated substrates. In contrast, depletion of Arf6 leads to intracellular accumulation of β1 integrin and reduced adhesion and spreading. These findings suggest that Arf6 regulates both endocytosis and recycling of β1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization. |
| Databáze: | OpenAIRE |
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