Characterization of KIF1C, a New Kinesin-like Protein Involved in Vesicle Transport from the Golgi Apparatus to the Endoplasmic Reticulum

doi:10.1074/jbc.273.32.20267

Characterization of KIF1C, a New Kinesin-like Protein Involved in Vesicle Transport from the Golgi Apparatus to the Endoplasmic Reticulum*

From the Department of Molecular Biology, Max-Planck Institut für Biochemie, Am Klopferspitz 18a, 82152 Martinsried, Germany

Abstract

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.

Footnotes

↵* This work was supported by a grant from Sugen Inc.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U91329 (KIF1C cDNA).
↵‡ Present address: Medical Clinic IV, University of Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany.
↵§ Present address: Max-Planck Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany.
↵¶ Present address: Novo-Nordisk, Novo Allee, 2880 Bagsværd, Denmark.
↵‖ To whom correspondence should be addressed. Tel.: 49-7071-2987599; Fax: 49-7071-295974; E-mail:rrlammer{at}med.uni-tuebingen.de.
↵2 S. Hollenberg and J. Cooper, unpublished results.
Abbreviations:

ER

endoplasmic reticulum

BFA

brefeldin A

KHC

kinesin heavy chain

KIF

kinesin family protein

KLP

kinesin-like protein

MT

microtubule

POV

peroxovanadate

PTP

protein-tyrosine phosphatase

PAGE

polyacrylamide gel electrophoresis.
- Received January 22, 1998.
- Revision received April 29, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.