The small GTP-binding ADP-ribosylation factor 1 (ARF1) acts as a master regulator of Golgi structure and function through the recruitment and activation of various downstream effectors. It has been proposed that members of the Rho family of small GTPases also control Golgi function in coordination with ARF1, possibly through the regulation of Arp2/3 complex and actin polymerization on Golgi membranes. Here, we identify ARHGAP10 — a novel Rho GTPase-activating protein (Rho-GAP) that is recruited to Golgi membranes through binding to GTP-ARF1. We show that ARHGAP10 functions preferentially as a GAP for Cdc42 and regulates the Arp2/3 complex and F-actin dynamics at the Golgi through the control of Cdc42 activity. Our results establish a role for ARHGAP10 in Golgi structure and function at the crossroads between ARF1 and Cdc42 signalling pathways.
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We are indebted to the Kazusa DNA Research Institute for the gift of the cDNA clone KIAA1424 and to D. Alessi for performing lipid overlay assay. We are grateful to E.G. Berger, J. Bertoglio, M. Bornens, V. W. Hsu, J. Wehland and I. Majoul for providing antibodies, and to D. Cassel, R. Cerione, A. Hall and P. Fort for plasmids. We would like to thank F. Perez and R. Pepperkok for helpful discussions throughout this study, and J. Plastino for critical reading of the manuscript. We also thank A. Letellier and C. Boulard for technical assistance. T.D. is the recipient of a post-doctoral fellowship from ARC (Association pour la Recherche sur le Cancer). This work was supported by an EC Training Network Grant HRPN-CT-2000-00081 (to P.C. and M.A.D.M.). Work in M.A.D.M.'s laboratory is supported by the Italian Association for Cancer Research (AIRC), Telethon Italia and the Italian Ministry for Universities and Research (MIUR). Work in P.C.'s laboratory is supported by grants from the CNRS, Institut Curie, La Fondation BNP-Paribas and La Ligue Nationale contre le Cancer ('équipe labellisée').
The authors declare no competing financial interests.
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Dubois, T., Paléotti, O., Mironov, A. et al. Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics. Nat Cell Biol 7, 353–364 (2005). https://doi.org/10.1038/ncb1244
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