UNC-16, a JNK-Signaling Scaffold Protein, Regulates Vesicle Transport in C. elegans

Abstract

Transport of synaptic components is a regulated process. Loss-of-function mutations in the C. elegans unc-16 gene result in the mislocalization of synaptic vesicle and glutamate receptor markers. unc-16 encodes a homolog of mouse JSAP1/JIP3 and Drosophila Sunday Driver. Like JSAP1/JIP3, UNC-16 physically interacts with JNK and JNK kinases. Deletion mutations in Caenorhabditis elegans JNK and JNK kinases result in similar mislocalization of synaptic vesicle markers and enhance weak unc-16 mutant phenotypes. unc-116 kinesin heavy chain mutants also mislocalize synaptic vesicle markers, as well as a functional UNC-16::GFP. Intriguingly, unc-16 mutations partially suppress the vesicle retention defect in unc-104 KIF1A kinesin mutants. Our results suggest that UNC-16 may regulate the localization of vesicular cargo by integrating JNK signaling and kinesin-1 transport.

A Scaffold Protein JIP-1b Enhances Amyloid Precursor Protein Phosphorylation by JNK and Its Association with Kinesin Light Chain 1

“…Furthermore, mutations in the UNC-16 protein, Caenorhabditis elegans homolog of JIP-3/JSAP1, result in the mislocalization of synaptic vesicle and glutamate receptor markers. Deletion mutations in C. elegans JNK and JNK kinases result in a similar mislocalization of synaptic vesicle markers (38). These observations suggest that JIP-3/JSAP1 and JNK signaling regulates the localization of vesicular cargo by kinesin-I transport.…”

JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16

“…Several orthologs of JNK pathway components have been characterized in C. elegans including: a mammalian JNK ortholog, jnk-1, two MKK4͞7 (JNK kinase) orthologs, jkk-1 and mek-1, and a JIP3 (scaffold protein) ortholog, unc-16 (16)(17)(18)(19). We started by examining the lifespan of loss-of-function mutants of jnk-1 and jkk-1.…”

Caenorhabditis elegans mom-4 is required for the activation of the p38 MAPK signaling pathway in the response to Pseudomonas aeruginosa infection

“…Genomic data of C. elegans was listed out the candidate components of the JNK and p38 pathways in C. elegans by comparison to mammalian homologs, and corresponding C. elegans mutants (Brenner et al, 1974;Kawasaki et al, 1999;Koga et al, 2000;Byrd et al, 2001;Sagasti et al, 2001;Sakaguchi et al, 2004;Nakata et al, 2005;Troemel et al, 2006). To confirm that jkk-1 is not involved in a response to the P. aeruginosa infection, and to find out whether other MAPKKKs and MAPKKs are involved in the response to pathogenic infections, we constructed RNAi plasmids for some of these candidate genes, as listed in Table 1.…”