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Vol. 11, Issue 10, 3441-3452, October 2000

Expression of Multiple UNC-13 Proteins in the Caenorhabditis elegans Nervous System

Rebecca Eustance Kohn,^* Janet S. Duerr,^* John R. McManus,^* Angie Duke,^* Terese L. Rakow,^§ Hiroko Maruyama,^§ Gary Moulder,^* Ichi N. Maruyama,^§ Robert J. Barstead,^* and James B. Rand^*

 ^*Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104; and  ^§Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037

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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Present address: Ursinus College, Collegeville, PA 19426.

These authors contributed equally to these studies.

Corresponding author. E-mail address: james-rand{at}omrf.ouhsc.edu.

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Molecular Biology of the Cell
Vol. 11, 3441-3452, October 2000
Copyright © 2000 by The American Society for Cell Biology

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