Expression of multiple UNC-13 proteins in the Caenorhabditis elegans nervous system

The Caenorhabditis elegans UNC-13 protein and its mammalian homologues are important for normal neurotransmitter release, We have identified a set of transcripts from the unc-13 locus in C. elegans resulting from alternative splicing and apparent alternative promoters. These transcripts encode prote ins that are identical in their C-terminal regions but that vary in their N -terminal regions. The most abundant protein form is localized to most or a ll synapses. We have analyzed the sequence alterations, immunostaining patt erns, and behavioral phenotypes of 31 independent unc-13 alleles. Many of t hese mutations are transcript-specific; their phenotypes suggest that the d ifferent UNC-13 forms have different cellular functions. We have also isola ted a deletion allele that is predicted to disrupt all UNC-13 protein produ cts; animals homozygous for this null allele are able to complete embryogen esis and hatch, but they die as paralyzed first-stage larvae. Transgenic ex pression of the entire gene rescues the behavior of mutants fully; transgen ic overexpression of one of the transcripts can partially compensate for th e genetic loss of another. This finding suggests some degree of functional overlap of the different protein products.