Journal of Cell Biology vol:186 issue:6 pages:897-914
Small GTPases of the Rab family regulate intracellular vesicular trafficking. In C. elegans, two dominant alleles of unc-108/rab-2 have been isolated based on their movement defects. Using a combination of pharmacological assays and electron microscopy, we show that the locomotion defects of rab-2 mutant animals are cause by a reduced facilitation of synaptic vesicle (SV) release from pre-synaptic sites due to lower levels of diacylglycerol (DAG). DAG levels at release sites can be regulated by neuro-peptides secreted from dense core vesicles (DCV). We show that while their number and distribution is not affected, DCVs in dominant rab-2 mutants are enlarged and contain less neuropeptides. This implicates RAB-2 in the biogenesis of DCVs at the Golgi complex. In rab-2 mutants DCV cargo inappropriately enters late endosomal compartments. Finally we show that RIC-19, the C. elegans ortholog of the human diabetes autoantigen ICA69, is recruited to Golgi membranes by RAB-2 for proper DCV biogenesis.