ADP-ribosylation factor 6 regulates actin cytoskeleton remodeling in coordination with Rac1 and RhoA

Boshans, R. L., Szanto, S., Van Aelst, L., D'Souza-Schorey, C. (May 2000) ADP-ribosylation factor 6 regulates actin cytoskeleton remodeling in coordination with Rac1 and RhoA. Molecular and Cellular Biology, 20 (10). pp. 3685-3694. ISSN 0270-7306

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10779358
DOI: 10.1128/mcb.20.10.3685-3694.2000

Abstract

In this study, we have documented an essential role for ADP-ribosylation factor 6 (ARF6) in cell surface remodeling in response to physiological stimulus and in the down regulation of stress fiber formation. We demonstrate that the G-protein-coupled receptor agonist bombesin triggers the redistribution of ARF6- and Rac1-containing endosomal vesicles to the cell surface. This membrane redistribution was accompanied by cortical actin rearrangements and was inhibited by dominant negative ARF6, implying that bombesin is a physiological trigger of ARF6 activation. Furthermore, these studies provide a new model for bombesin-induced Rac1 activation that involves ARF6-regulated endosomal recycling. The bombesin-elicited translocation of vesicular ARF6 was mimicked by activated G alpha q and was partially inhibited by expression of RGS2, which down regulates Gq function. This suggests that Gq functions as an upstream regulator of ARF6 activation. The ARF6-induced peripheral cytoskeletal rearrangements were accompanied by a depletion of stress fibers. Moreover, cells expressing activated ARF6 resisted the formation of stress fibers induced by lysophosphatidic acid. We show that the ARF6-dependent inhibition of stress fiber formation was due to an inhibition of RhoA activation and was overcome by expression of a constitutively active RhoA mutant. The latter observations demonstrate that activation of ARF6 down regulates Rho signaling. Our findings underscore the potential roles of ARF6, Rac1, and RhoA in the coordinated regulation of cytoskeletal remodeling.

Item Type: Paper
Uncontrolled Keywords: GTP-BINDING-PROTEIN RECEPTOR-MEDIATED ENDOCYTOSIS PHOSPHOLIPASE-D PLASMA-MEMBRANE EXCHANGE FACTOR RAC1-INTERACTING PROTEIN LYSOPHOSPHATIDIC ACID STRESS FIBERS P115 RHOGEF KINASE-C
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Rho
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > actin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cytoskeletal proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
Depositing User: Matt Covey
Date: May 2000
Date Deposited: 18 Dec 2013 21:45
Last Modified: 18 Dec 2013 21:45
PMCID: PMC85663
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29105

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