Characterization of KIF1C, a new kinesin-like protein involved in vesicle transport from the Golgi apparatus to the endoplasmic reticulum.
Kinesins comprise a large family of microtubule-based motor proteins, of which individual members mediate specific types of motile processes. Using the ezrin domain of the protein-tyrosine phosphatase PTPD1 as a bait in a yeast two-hybrid screen, we identified a new kinesin-like protein, KIF1C. KIF1C represents a member of the Unc104 subfamily of kinesin-like proteins that are involved in the transport of mitochondria or synaptic vesicles in axons. Like its homologues, the 1103-amino acid protein KIF1C consists of an amino-terminal motor domain followed by a U104 domain and probably binds to target membranes through carboxyl-terminal sequences. Interestingly, KIF1C was tyrosine-phosphorylated after peroxovanadate stimulation when overexpressed in 293 or NIH3T3 fibroblasts or in native C2C12 cells. Using immunofluorescence, we found that KIF1C is localized primarily at the Golgi apparatus. In brefeldin A-treated cells, the Golgi membranes and KIF1C redistributed to the endoplasmic reticulum (ER). This brefeldin A-induced flow of Golgi membranes into the ER was inhibited in cells transiently overexpressing catalytically inactive KIF1C. In conclusion, our data suggest an involvement of tyrosine phosphorylation in the regulation of the Golgi to ER membrane flow and describe a new kinesin-like motor protein responsible for this transport.
Department of Molecular Biology, Max-Planck Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany.
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Dorner
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Ciossek
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Müller
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Møller
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Ullrich
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Lammers
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020126:Brefeldin A; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000502:physiology*; D006801:Humans; D016547:Kinesins / Q000737:chemistry*; D018942:Macrolides; D051379:Mice; D008870:Microtubules / Q000737:chemistry*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; C114063:KIF1C protein, human; C485246:Kif1c protein, mouse; D018942:Macrolides; D012333:RNA, Messenger; D020126:Brefeldin A; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases; C000602628:KIF1C protein, rat; D016547:Kinesins