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Originally published as MBC in Press, 10.1091/mbc.E04-07-0553 on November 24, 2004

Vol. 16, Issue 2, 483-496, February 2005

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The Caenorhabditis elegans UNC-14 RUN Domain Protein Binds to the Kinesin-1 and UNC-16 Complex and Regulates Synaptic Vesicle Localization{boxd}

Rie Sakamoto * {dagger}, Dana T. Byrd {dagger} {ddagger} §, Heather M. Brown {ddagger}, Naoki Hisamoto *, Kunihiro Matsumoto *, and Yishi Jin {ddagger}

* Department of Molecular Biology, Graduate School of Science, Nagoya University and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Nagoya 464-8602, Japan; {ddagger} Department of Molecular Cell and Development Biology, Sinsheimer Laboratories, Howard Hughes Medical Institute, University of California, Santa Cruz, Santa Cruz, CA 95064

Submitted July 4, 2004; Accepted November 10, 2004
Monitoring Editor: Suzanne Pfeffer

Kinesin-1 is a heterotetramer composed of kinesin heavy chain (KHC) and kinesin light chain (KLC). The Caenorhabditis elegans genome has a single KHC, encoded by the unc-116 gene, and two KLCs, encoded by the klc-1 and klc-2 genes. We show here that UNC-116/KHC and KLC-2 form a complex orthologous to conventional kinesin-1. KLC-2 also binds UNC-16, the C. elegans JIP3/JSAP1 JNK-signaling scaffold protein, and the UNC-14 RUN domain protein. The localization of UNC-16 and UNC-14 depends on kinesin-1 (UNC-116 and KLC-2). Furthermore, mutations in unc-16, klc-2, unc-116, and unc-14 all alter the localization of cargos containing synaptic vesicle markers. Double mutant analysis is consistent with these four genes functioning in the same pathway. Our data support a model whereby UNC-16 and UNC-14 function together as kinesin-1 cargos and regulators for the transport or localization of synaptic vesicle components.


Article published online ahead of print in MBC in Press on November 24, 2004 (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E04-07-0553).

{boxd} The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

{dagger} These authors contributed equally to this work.

§ Present address: Howard Hughes Medical Institute, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.

Address correspondence to: Yishi Jin (Jin{at}biology.ucsc.edu) or Kunihiro Matsumoto (g44177a{at}nucc.cc.nagoya-tt.ac.jp).




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