IA-2, a major autoantigen in type 1 diabetes, is a receptor-tyrosine phosphatase-like protein associated with the membrane of secretory granules of neural and endocrine-specific cells. IA-2 lacks phosphatase activity due to an amino acid substitution within the catalytic domain and the function of IA-2 remains unclear. In order to gain insight into the cellular functions of IA-2, we have studied the C. elegans homolog, CeIA-2 encoded by the
ida-1 gene. Using two independent, putative null, deletion alleles of
ida-1 we show that animals lacking CeIA-2 are viable with only subtle visible phenotypes. Pharmacological studies show loss of CeIA-2 results in presynaptic neuronal defects involving neurotransmitter release. Furthermore,
ida-1 interacts genetically with
unc-31 and
unc-64, two genes encoding factors required for neuronal vesicle function. These results suggest that CeIA-2 is a novel regulator of synaptic transmission that regulates vesicle release.