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A role for the Rab6A′ GTPase in the inactivation of the Mad2‐spindle checkpoint
Author(s) -
MisereyLenkei Stéphanie,
CouëdelCourteille Anne,
Del Nery Elaine,
Bardin Sabine,
Piel Matthieu,
Racine Victor,
Sibarita JeanBaptiste,
Perez Franck,
Bornens Michel,
Goud Bruno
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600929
Subject(s) - biology , mad2 , spindle checkpoint , gtpase , g2 m dna damage checkpoint , microbiology and biotechnology , cell cycle checkpoint , genetics , computational biology , spindle apparatus , cell cycle , gene , cell division , cell
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 p150 Glued , 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 p150 Glued and GAPCenA, may thus participate in a pathway involved in the metaphase/anaphase transition.