The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization

• Published in: Molecular biology of the cell 2005-02, Vol.16 (2), p.483-496
• Main Authors: Sakamoto, Rie, Byrd, Dana T, Brown, Heather M, Hisamoto, Naoki, Matsumoto, Kunihiro, Jin, Yishi
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - chemistry; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Amino Acid Sequence; Animals; Blotting, Western; Caenorhabditis elegans - genetics; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Fluorescent Antibody Technique, Indirect; Gene Expression; Genes, Helminth; Green Fluorescent Proteins - analysis; Humans; Kinesin - metabolism; Models, Genetic; Molecular Sequence Data; Mutation; Neurons - metabolism; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Synaptic Vesicles - metabolism; Transgenes; Two-Hybrid System Techniques; Vesicular Transport Proteins - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E04-07-0553

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.