title: Rab6 regulation of the kinesin family KIF1C motor domain contributes to Golgi tethering.
abstract: Most kinesins transport cargoes bound to their C-termini and use N-terminal motor domains to move along microtubules. We report here a novel function for KIF1C: it transports Rab6A-vesicles and can influence Golgi complex organization. These activities correlate with KIF1C's capacity to bind the Golgi protein Rab6A directly, both via its motor domain and C-terminus. Rab6A binding to the motor domain inhibits microtubule interaction in vitro and in cells, decreasing the amount of motile KIF1C. KIF1C depletion slows protein delivery to the cell surface, interferes with vesicle motility, and triggers Golgi fragmentation. KIF1C can protect Golgi membranes from fragmentation in cells lacking an intact microtubule network. Rescue of fragmentation requires sequences that enable KIF1C to bind Rab6A at both ends, but not KIF1C motor function. Rab6A binding to KIF1C's motor domain represents an entirely new mode of regulation for a kinesin motor, and likely has important consequences for KIF1C's cellular functions.
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
authors.forename: Peter L
authors.identifier: http://orcid.org/0000-0002-5553-9041
authors.initials: PL
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
authors.forename: Maikke B
authors.initials: MB
authors.lastname: Ohlson
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
authors.forename: Suzanne R
authors.identifier: http://orcid.org/0000-0002-6462-984X
authors.initials: SR
authors.lastname: Pfeffer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D059008:Time-Lapse Imaging; D014162:Transfection; D014709:Vero Cells; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C114063:KIF1C protein, human; C094135:Rab6 protein; D016547:Kinesins; D020691:rab GTP-Binding Proteins; D015739:Nocodazole
keywords: Golgi complex; KIF1C; Rab GTPase; biochemistry; cell biology; kinesin; microtubule motor; none
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