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Vol. 13, Issue 3, 866-879, March 2002



*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; 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(
Departamento de Biología
Celular, Facultad de Medicina, Universidad de Murcia, E-30071 Murcia,
Spain; and §Imperial Cancer Research Fund, London Wc2A
3PX, England
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.
Present address: DPC Dipesa, Dept.
Técnico-Científico, 08029 Barcelon, Spain.
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