Article
- The EMBO Journal (2006) 25, 278 - 289
- doi:10.1038/sj.emboj.7600929
Published online: 5 January 2006
Subject Categories:
A role for the Rab6A' GTPase in the inactivation of the Mad2-spindle checkpoint
Stéphanie Miserey-Lenkei, Anne Couëdel-Courteille, Elaine Del Nery, Sabine Bardin, Matthieu Piel, Victor Racine, Jean-Baptiste Sibarita, Franck Perez, Michel Bornens and Bruno Goud
- UMR 144 CNRS/IC, Institut Curie, Paris, France
Correspondence to:
Bruno Goud, UMR 144 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France. Tel.: +33 1 4234 6398; Fax: +33 1 4234 6382; E-mail: bruno.goud@curie.fr
Received 1 August 2005; Accepted 30 November 2005
Abstract
The two isoforms of the Rab6 GTPase, Rab6A and Rab6A', regulate a retrograde transport route connecting early endosomes and the endoplasmic reticulum via the Golgi complex in interphasic cells. Here we report that when Rab6A' function is altered cells are unable to progress normally through mitosis. Such cells are blocked in metaphase, despite displaying a normal Golgi fragmentation and with the Mad2-spindle checkpoint activated. Furthermore, the Rab6 effector p150Glued, a subunit of the dynein/dynactin complex, remains associated with some kinetochores. A similar phenotype was observed when GAPCenA, a GTPase-activating protein of Rab6, was depleted from cells. Our results suggest that Rab6A' likely regulates the dynamics of the dynein/dynactin complex at the kinetochores and consequently the inactivation of the Mad2-spindle checkpoint. Rab6A', through its interaction with p150Glued and GAPCenA, may thus participate in a pathway involved in the metaphase/anaphase transition.
Keywords:
- dynein/dynactin complex,
- GAPCenA,
- metaphase,
- Rab6 GTPase,
- spindle checkpoint
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