We are investigating the roles of UNC-13 in synaptic transmission and signal transduction. Unc-13 is essential for normal neuronal function and is thought to be involved in neurotransmitter release; C. elegans mutants are uncoordinated and resistant to the anti-cholinesterase aldicarb. UNC- 13 has several regions homologous to PKC regulatory domains, which confer UNC-13 with phorbol ester and phospholipid binding properties (Maruyama and Brenner, PNAS 88:5729, 1991). We have identified at least two types of
unc-13 transcripts. They appear to be transcribed from different promoters and encode proteins with different N-terminal domains. On Northern transfers, these transcripts appear to be 5.9 kb and 4.9 kb in length. To date, ten of the >40
unc-13 alleles in our collection have been sequenced. Two of the mutations (Maruyama and Brenner, PNAS 88:5729, 1991) are located in the 5' end of the gene (both mutants are paralyzed and one has a slightly coily phenotype). Eight newly sequenced mutations in the 3' end of the gene represent a different phenotypic class. These mutants are paralyzed and most are more coily and slower growing than alleles with mutations in the 5' region. A lethal phenotype results from a 2.7 kb deletion at the 3' end of
unc-13; L1 larvae hatch and remain tightly coiled, but do not grow, and eventually die. Antibodies recognizing the N terminal region of
unc-13 label synapses (but not synaptic vesicles) of most or all neurons. Many
unc-13 alleles have decreased staining with this antibody. Antibodies recognizing the C terminal region (common to all predicted UNC-13 proteins) label synapses and neuronal processes of most or all neurons. This staining pattern decreases in only three alleles, all of which are lethal or partially lethal. The existence of more than one
unc-13 transcript, the different phenotypic classes resulting from mutations in either the 5' or 3' end of
unc-13 and the alternate staining patterns with anti-UNC-13 antibodies all suggest that protein products from
unc-13 have different expression or localization patterns and possibly different functions.