A role for Arf1 in mitotic Golgi disassembly, chromosome segregation, and cytokinesis.
In mitosis, chromosome, cytoskeleton, and organelle dynamics must be coordinated for successful cell division. Here, we present evidence for a role for Arf1, a small GTPase associated with the Golgi apparatus, in the orchestration of mitotic Golgi breakdown, chromosome segregation, and cytokinesis. We show that early in mitosis Arf1 becomes inactive and dissociates from Golgi membranes. This is followed by the dispersal of numerous Arf1-dependent peripheral Golgi proteins and subsequent Golgi disassembly. If Arf1 is kept in an active state by treatment with the small molecule H89 or expression of its GTP-locked form, intact Golgi membranes with bound peripheral proteins persist throughout mitosis. These cells enter mitosis but exhibit gross defects in chromosome segregation and cytokinetic furrow ingression. These findings suggest that mitotic Golgi disassembly depends on Arf1 inactivation and is used by the cell to disperse numerous peripheral Golgi proteins for coordinating the behavior of Golgi membranes, chromosomes, and cytoskeleton during mitosis.
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Nihal
N
Altan-Bonnet
Robert D
RD
Phair
Roman S
RS
Polishchuk
Roberto
R
Weigert
Jennifer
J
Lippincott-Schwartz
D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D020090:Chromosome Segregation; D002875:Chromosomes / Q000648:ultrastructure*; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D018613:Microscopy, Confocal; D008938:Mitosis; D010957:Plasmids / Q000378:metabolism; D013449:Sulfonamides; D013997:Time Factors
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D020823:ADP-Ribosylation Factor 1; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide