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Journal of Cell Science, Vol 112, Issue 6 855-866, Copyright © 1999 by Company of Biologists

JOURNAL ARTICLES

ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements

H Radhakrishna, O Al-Awar, Z Khachikian and JG Donaldson
Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA.

The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling. Here we examined the relationship between ARF6 and Rac1, a Rho family GTPase, implicated in cortical actin rearrangements. Endogenous Rac1 colocalized with ARF6 at the plasma membrane and on the ARF6 recycling endosome in untransfected HeLa and primary human fibroblast cells. In transfected HeLa cells Rac1 and ARF6 also colocalized. Cells expressing wild-type ARF6 or Rac1 formed actin-containing surface protrusions and membrane ruffles, respectively, upon treatment with the G protein activator aluminum fluoride. Aluminum fluoride-treatment of cells transfected with equivalent amounts of plasmid resulted in enhanced membrane ruffling, with protrusions appearing as Rac expression was lowered. Co-expression of the dominant negative, GTP binding-defective ARF6 T27N mutant inhibited the aluminum fluoride-induced ruffling observed in cells expressing Rac1, and the constitutive ruffling observed in cells expressing the activated Rac1 Q61L mutant. In contrast, co-expression of the GTP-binding-defective, T17N mutant of either Rac1 or Cdc42 with ARF6 did not inhibit the aluminum fluoride-induced surface protrusions, nor did inactivation of Rho with C3-transferase. These observations suggest that ARF6, a non-Rho family GTPase, can, by itself, alter cortical actin and can influence the ability of Rac1 to form lamellipodia, in part, by regulating its trafficking to the plasma membrane.
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H. Uchida, A. Kondo, Y. Yoshimura, Y. Mazaki, and H. Sabe
Pag3/Pap{alpha}/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fc{gamma} Receptor-Mediated Phagocytosis of Macrophages
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C. Krawczyk and J. M. Penninger
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An ADP-Ribosylation Factor GTPase-activating Protein Git2-short/KIAA0148 Is Involved in Subcellular Localization of Paxillin and Actin Cytoskeletal Organization
Mol. Biol. Cell, March 1, 2001; 12(3): 645 - 662.
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Y. Takai, T. Sasaki, and T. Matozaki
Small GTP-Binding Proteins
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T. R. Jackson, F. D. Brown, Z. Nie, K. Miura, L. Foroni, J. Sun, V. W. Hsu, J. G. Donaldson, and P. A. Randazzo
Acaps Are Arf6 Gtpase-Activating Proteins That Function in the Cell Periphery
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D. K. Meyer, C. Olenik, F. Hofmann, H. Barth, J. Leemhuis, I. Brunig, K. Aktories, and W. Norenberg
Regulation of Somatodendritic GABAA Receptor Channels in Rat Hippocampal Neurons: Evidence for a Role of the Small GTPase Rac1
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O. Al-Awar, H. Radhakrishna, N. N. Powell, and J. G. Donaldson
Separation of Membrane Trafficking and Actin Remodeling Functions of ARF6 with an Effector Domain Mutant
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M. E. Martin, J. Hidalgo, J. L. Rosa, P. Crottet, and A. Velasco
Effect of Protein Kinase A Activity on the Association of ADP-ribosylation Factor 1 to Golgi Membranes
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R. L. Boshans, S. Szanto, L. van Aelst, and C. D'Souza-Schorey
ADP-Ribosylation Factor 6 Regulates Actin Cytoskeleton Remodeling in Coordination with Rac1 and RhoA
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J. G. Donaldson
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A New Paxillin-binding Protein, PAG3/Papalpha /KIAA0400, Bearing an ADP-Ribosylation Factor GTPase-activating Protein Activity, Is Involved in Paxillin Recruitment to Focal Adhesions and Cell Migration
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Q. Zhang, J. Calafat, H. Janssen, and S. Greenberg
ARF6 Is Required for Growth Factor- and Rac-Mediated Membrane Ruffling in Macrophages at a Stage Distal to Rac Membrane Targeting
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M. A. Sells, J. T. Boyd, and J. Chernoff
p21-Activated Kinase 1 (Pak1) Regulates Cell Motility in Mammalian Fibroblasts
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From the Cover: The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton
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G. Scita, P. Tenca, L. B. Areces, A. Tocchetti, E. Frittoli, G. Giardina, I. Ponzanelli, P. Sini, M. Innocenti, and P. P. Di Fiore
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L. C. Santy and J. E. Casanova
Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D
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D. J. Powner, M. N. Hodgkin, and M. J.O. Wakelam
Antigen-stimulated Activation of Phospholipase D1b by Rac1, ARF6, and PKCalpha in RBL-2H3 Cells
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R. V. Fucini, J.-L. Chen, C. Sharma, M. M. Kessels, and M. Stamnes
Golgi Vesicle Proteins Are Linked to the Assembly of an Actin Complex Defined by mAbp1
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