The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta-1 integrins

Jillian Dunphy, Radim Moravec, Kim Ly, Lasell Troy K., Paul Melancon, James E. Casanova

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


The small GTPase Arf6 has been shown to regulate the post-endocytic trafficking of a subset of membrane proteins, including ß1 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 ß1 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 ß1 integrin and reduced adhesion and spreading. These findings suggest that Arf6 regulates both endocytosis and recycling of ß1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization.
Original languageEnglish
Pages (from-to)315-320
Number of pages6
JournalCurrent Biology
Issue number3
Publication statusPublished - 2006


Dive into the research topics of 'The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta-1 integrins'. Together they form a unique fingerprint.

Cite this