Worm Breeder's Gazette 17(2): 32 (April 1, 2002)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
| 1 | Division of Biological Science, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, JAPAN |
| 2 | University of California, Santa Cruz, Dept. Biol., Sinsheimer Labs, CA 95064 USA |
The c-Jun N-terminal kinase (JNK) of the MAP kinase (MAPK) superfamily is involved in various stress responses and apoptosis in mammal. The C. elegans JNK cascade is composed of JNK-1 (MAPK) and JKK-1 (MAPKK). The JNK-1 pathway functions in type-D GABAergic motor neuron and modulates coordinated locomotion. The C. elegans unc-16 gene encodes a protein homologous to mammalian JSAP1/JIP3, which acts as a scaffold protein in the JNK pathway by binding with MLK (MAPKKK), MKK7 (MAPKK) and JNK3 (MAPK). Like JSAP1/JIP3, UNC-16 physically interacts with JNK-1 and JKK-1, forming a JNK signaling module. unc-16(ju79), jnk-1(gk7), and jkk-1(km2) mutant animals exhibit mislocalization of synaptic vesicle marker SNB-1::GFP in L1 DD motor neurons. This suggests that the JNK-1 pathway containing UNC-16 regulates synaptic vesicle localization.
To understand the mechanism regulated by UNC-16, we screened for UNC-16-binding proteins using yeast two-hybrid system. One of the isolated genes is klc-2 encoding a kinesin light chain. Co-immunoprecipitation experiments reveal that KLC-2 associates with UNC-16 and UNC-116 kinesin heavy chain when they are co-expressed in mammalian cells. We constructed the klc-2(km11) mutation that produces a truncated form of the KLC-2 protein lacking its C-terminal portion. The mutant animals exhibit Unc and weak Dpy phenotypes. Similar to unc-16(ju79), jnk-1(gk7), and jkk-1(km2) mutants, the SNB-1::GFP marker is mislocalized along the dorsal DD processes in the klc-2(km11) L1 larvae. These results raise the possibility that the UNC-16-JNK-1 pathway regulates synaptic vesicle localization through phosphorylation of KLC-2 in C. elegans.