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Originally published as MBC in Press, 10.1091/mbc.01-12-0579 on February 4, 2002
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Vol. 13, Issue 3, 866-879, March 2002

Regulation of Protein Transport from the Golgi Complex to the Endoplasmic Reticulum by CDC42 and N-WASP

Ana Luna,*dagger Olga B. Matas,* José Angel Martínez-Menárguez,Dagger Eugenia Mato,* Juan M. Durán,* José Ballesta,Dagger Michael Way,§ and Gustavo Egea*||

 *Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, E-08036 Barcelona, Spain;  Dagger Departamento de Biología Celular, Facultad de Medicina, Universidad de Murcia, E-30071 Murcia, Spain; and  §Imperial Cancer Research Fund, London Wc2A 3PX, England

Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and noncoated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgi-to-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(Delta WA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-N-WASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP-dependent manner.


|| Corresponding author. E-mail address: egea{at}medicina.ub.es.

dagger Present address: DPC Dipesa, Dept. Técnico-Científico, 08029 Barcelon, Spain.


Molecular Biology of the Cell
Vol. 13, 866-879, March 2002
Copyright © 2002 by The American Society for Cell Biology



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