A role for the Rab6A’ GTPase in the inactivation of the Mad2-spindle checkpoint
EMBO J.. 2006 Jan 25; 25(2): 278-89
DOI: 7600929 [pii]10.1038/sj.emboj.7600929
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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.
DOI: 10.1038/sj.emboj.7600929
PMCID: PMC1383512
PMID: 16395330 [Indexed for MEDLINE]