Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 11, Issue 10, Pages 3441-3452Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.11.10.3441
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- NIGMS NIH HHS [R01 GM059642] Funding Source: Medline
- NINDS NIH HHS [NS31439, NS33187] Funding Source: Medline
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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 proteins 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 all synapses. We have analyzed the sequence alterations, immunostaining patterns, and behavioral phenotypes of 31 independent unc-13 alleles. Many of these mutations are transcript-specific; their phenotypes suggest that the different UNC-13 forms have different cellular functions. We have also isolated a deletion allele that is predicted to disrupt all UNC-13 protein products; animals homozygous for this null allele are able to complete embryogenesis and hatch, but they die as paralyzed first-stage larvae. Transgenic expression of the entire gene rescues the behavior of mutants fully; transgenic overexpression of one of the transcripts can partially compensate for the genetic loss of another. This finding suggests some degree of functional overlap of the different protein products.
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