A Role for the Rab6A' GTPase in the Inactivation of the Mad2-spindle Checkpoint

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Jan 6

PMID 16395330

Citations 41

Authors

Stephanie Miserey-Lenkei

Anne Couedel-Courteille

Elaine Del Nery

Sabine Bardin

Matthieu Piel

Victor Racine

Jean-Baptiste Sibarita

Franck Perez

Michel Bornens

Bruno Goud

Affiliations

Soon will be listed here.

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 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.

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References

Rojo M, Legros F, Chateau D, Lombes A . Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci. 2002; 115(Pt 8):1663-74. DOI: 10.1242/jcs.115.8.1663. View

Brummelkamp T, Bernards R, Agami R . A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002; 296(5567):550-3. DOI: 10.1126/science.1068999. View

Sutterlin C, Hsu P, Mallabiabarrena A, Malhotra V . Fragmentation and dispersal of the pericentriolar Golgi complex is required for entry into mitosis in mammalian cells. Cell. 2002; 109(3):359-69. DOI: 10.1016/s0092-8674(02)00720-1. View

Guertin D, Trautmann S, McCollum D . Cytokinesis in eukaryotes. Microbiol Mol Biol Rev. 2002; 66(2):155-78. PMC: 120788. DOI: 10.1128/MMBR.66.2.155-178.2002. View

Peters J . The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell. 2002; 9(5):931-43. DOI: 10.1016/s1097-2765(02)00540-3. View

Canman J, Salmon E, Fang G . Inducing precocious anaphase in cultured mammalian cells. Cell Motil Cytoskeleton. 2002; 52(2):61-5. DOI: 10.1002/cm.10032. View

Musacchio A, Hardwick K . The spindle checkpoint: structural insights into dynamic signalling. Nat Rev Mol Cell Biol. 2002; 3(10):731-41. DOI: 10.1038/nrm929. View

Shorter J, Warren G . Golgi architecture and inheritance. Annu Rev Cell Dev Biol. 2002; 18:379-420. DOI: 10.1146/annurev.cellbio.18.030602.133733. View

Karki S, Holzbaur E . Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. J Biol Chem. 1995; 270(48):28806-11. DOI: 10.1074/jbc.270.48.28806. View

10.

Goud B, Zahraoui A, Tavitian A, Saraste J . Small GTP-binding protein associated with Golgi cisternae. Nature. 1990; 345(6275):553-6. DOI: 10.1038/345553a0. View

11.

Bailly E, McCaffrey M, Touchot N, Zahraoui A, Goud B, Bornens M . Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2. Nature. 1991; 350(6320):715-8. DOI: 10.1038/350715a0. View

12.

Antony C, Cibert C, Geraud G, Maria A, Maro B, Mayau V . The small GTP-binding protein rab6p is distributed from medial Golgi to the trans-Golgi network as determined by a confocal microscopic approach. J Cell Sci. 1992; 103 ( Pt 3):785-96. DOI: 10.1242/jcs.103.3.785. View

13.

Martinez O, Schmidt A, Salamero J, Hoflack B, Roa M, Goud B . The small GTP-binding protein rab6 functions in intra-Golgi transport. J Cell Biol. 1994; 127(6 Pt 1):1575-88. PMC: 2120294. DOI: 10.1083/jcb.127.6.1575. View

14.

Preisinger C, Korner R, Wind M, Lehmann W, Kopajtich R, Barr F . Plk1 docking to GRASP65 phosphorylated by Cdk1 suggests a mechanism for Golgi checkpoint signalling. EMBO J. 2005; 24(4):753-65. PMC: 549625. DOI: 10.1038/sj.emboj.7600569. View

15.

Gromley A, Yeaman C, Rosa J, Redick S, Chen C, Mirabelle S . Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell. 2005; 123(1):75-87. DOI: 10.1016/j.cell.2005.07.027. View

16.

Langevin J, Morgan M, Sibarita J, Aresta S, Murthy M, Schwarz T . Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane. Dev Cell. 2005; 9(3):365-76. DOI: 10.1016/j.devcel.2005.07.013. View

17.

Siller K, Serr M, Steward R, Hays T, Doe C . Live imaging of Drosophila brain neuroblasts reveals a role for Lis1/dynactin in spindle assembly and mitotic checkpoint control. Mol Biol Cell. 2005; 16(11):5127-40. PMC: 1266413. DOI: 10.1091/mbc.e05-04-0338. View

18.

Del Nery E, Miserey-Lenkei S, Falguieres T, Nizak C, Johannes L, Perez F . Rab6A and Rab6A' GTPases play non-overlapping roles in membrane trafficking. Traffic. 2006; 7(4):394-407. DOI: 10.1111/j.1600-0854.2006.00395.x. View

19.

White J, Johannes L, Mallard F, Girod A, Grill S, Reinsch S . Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells. J Cell Biol. 1999; 147(4):743-60. PMC: 2156170. DOI: 10.1083/jcb.147.4.743. View

20.

Zaal K, Smith C, Polishchuk R, Altan N, Cole N, Ellenberg J . Golgi membranes are absorbed into and reemerge from the ER during mitosis. Cell. 1999; 99(6):589-601. DOI: 10.1016/s0092-8674(00)81548-2. View