Localization of synaptic components must be both precise and dynamic to allow proper information flow between neurons and their targets. In first larval stage (L1) animals, the GABAergic DD motor neurons form synapses with ventral body wall muscle, and the localization of SNB-1::GFP, a synaptic vesicle marker, is restricted to the ventral processes. Loss-of-function mutations in the
unc-16 gene result in the mislocalization of SNB-1::GFP to dorsal dendritic processes of L1 stage DD neurons without a detectable change in a postsynaptic GABA receptor marker in the muscle. The localization of presynaptic markers in many neurons is similarly altered in
unc-16 mutants. SNB-1::GFP is mislocalized to the dorsal dendritic processes of the VD motor neurons and out along the dendritic endings of several sensory neurons in the head. Intriguingly, GLR-1::GFP, a postsynaptic marker, is also mislocalized along the ventral cord and in the anterior endings of some interneurons.
unc-16 encodes a protein homologous to mouse JSAP1/JIP3 and Drosophila Sunday Driver (dSYD). Like its mammalian homologs, UNC-16 physically interacts with JNK signaling components. Deletion mutants of KNK signaling genes result in slight mislocalization of synaptic vesicle markers in L1 DD motor neurons and exacerbate the phenotype of weak
unc-16 alleles. UNC-16 and JNK signaling molecules are expressed in neurons and function cell autonomously in DD neurons. Our results suggest that UNC-16 may regulate synaptic vesicle transport through its combined interactions with both JNK signaling molecules and motor proteins. In support of a role for UNC-16 in regulating vesicle transport,
unc-16 mutations partially suppress mutations in
unc-104 , a synaptic vesicle specific kinesin. The suppression is not allele specific, suggesting that the interaction of
unc-16 and
unc-104 may not be direct, but that both UNC-104 and UNC-16 may contribute to a similar process. Mutations in
unc-16 do not suppress
unc-116 kinesin heavy chain mutations. Instead, a weak
unc-116 mutation results in SNB-1::GFP mislocalization in L1 DD motor neurons similar to that seen in
unc-16 mutants. We propose that UNC-16 functions by both forming a linkage between vesicular cargo and motor proteins and serving as a scaffold for signaling molecules that direct cargo selection, motor activity, or motor direction.