ARAP2 effects on the actin cytoskeleton are dependent on Arf6-specific GTPase-activating-protein activity and binding to RHoA-GTP

Hye Young Yoon, Koichi Miura, E. Jebb Cuthbert, Kathryn Kay Davis, Bijan Ahvazl, James E. Casanova, Paul A. Randazzo

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

ARAP2 is a protein that contains both ArfGAP and RhoGAP domains. We found that it is a phosphatidylinositol (3,4,5)-trisphosphate-dependent Arf6 GAP that binds RhoA-GTP but lacks RhoGAP activity. In agreement with the hypothesis that ARAP2 mediates effects of RhoA, endogenous ARAP2 associated with focal adhesions (FAs) and reduction of ARAP2 expression, by RNAi, resulted in fewer FAs and actin stress fibers (SFs). In cells with reduced levels of endogenous ARAP2, FAs and SFs could be restored with wild-type recombinant ARAP2 but not mutants lacking ArfGAP or Rho-binding activity. Constitutively active Arf6 also caused a loss of SFs. The Rho effector ROKα was ineffective in restoring FAs. Conversely, overexpression of ARAP2 did not restore SFs in cells treated with a ROK inhibitor but induced punctate accumulations of paxillin. We conclude that ARAP2 is an Arf6GAP that functions downstream of RhoA to regulate focal adhesion dynamics.

Original languageEnglish
Pages (from-to)4650-4666
Number of pages17
JournalJournal of cell science
Volume119
Issue number22
DOIs
Publication statusPublished - Nov 15 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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