OBJECTIVE: To investigate whether genes required for synaptogenesis and synaptic function are also involved in fat storage control in Caenorhabditis elegans. METHODS: Fat storage was examined in mutants of genes affecting the synaptogenesis and synaptic function. In addition, the genetic interactions of SNAREs syntaxin/unc-64 and SNAP-25/ric-4 with
daf-2,
daf-7,
nhr-49,
sbp-1 and
mdt-15 in regulating fat storage were further investigated. The tissue-specific activities of
unc-64 and
ric-4 were investigated to study the roles of
unc-64 and
ric-4 in regulating fat storage in the nervous system and/or the intestine. RESULTS: Mutations of genes required for the formation of presynaptic neurotransmission site did not obviously influence fat storage. However, among the genes required for synaptic function, the plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 genes were involved in the fat storage control. Fat storage in the intestinal cells was dramatically increased in
unc-64 and
ric-4 mutants as revealed by Sudan Black and Nile Red strainings, although the fat droplet size was not significantly changed. Moreover, in both the nervous system and the intestine, expression of
unc-64 significantly inhibited the increase in fat storage observed in
unc-64 mutant. And expression of
ric-4 in the nervous system completely restored fat storage in
ric-4 mutant. Genetic interaction assay further indicated that both
unc-64 and
ric-4 regulated fat storage independently of
daf-2 [encoding an insulin-like growth factor-I (IGF-I) receptor],
daf-7 [encoding a transforming growth factor-beta (TGF-beta) ligand], and
nhr-49 (encoding a nuclear hormone receptor). Besides, mutation of
daf-16 did not obviously affect the phenotype of increased fat storage in
unc-64 or
ric-4 mutant. Furthermore,
unc-64 and
ric-4 regulated fat storage probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways. In addition, fat storage in
unc-64;
ric-4 was higher than that in either
unc-64 or
ric-4 single mutant nematodes, suggesting that
unc-64 functions in parallel with
ric-4 in regulating fat storage. CONCLUSION: The plasma membrane-associated SNAREs syntaxin/unc-64 and SNAP-25/ric-4 function in parallel in regulating fat storage in C. elegans, probably through the ARC105/mdt-15- and SREBP/sbp-1-mediated signaling pathways.