A role for the Rab6A' GTPase in the inactivation of the Mad2-spindle checkpoint.
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.
Miserey-Lenkei
Stéphanie
S
UMR 144 CNRS/IC, Institut Curie, Paris, France.
Couëdel-Courteille
Anne
A
Del Nery
Elaine
E
Bardin
Sabine
S
Piel
Matthieu
M
Racine
Victor
V
Sibarita
Jean-Baptiste
JB
Perez
Franck
F
Bornens
Michel
M
Goud
Bruno
B
D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D064246:Mad2 Proteins; D008677:Metaphase / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D020690:GTPase-Activating Proteins; D007527:Isoenzymes; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; C119053:RABGAP1 protein, human; C094135:Rab6 protein; D012097:Repressor Proteins; D020691:rab GTP-Binding Proteins