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.