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 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.
Kohn
R E
RE
Program in Molecular and Cell Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Duerr
J S
JS
McManus
J R
JR
Duke
A
A
Rakow
T L
TL
Maruyama
H
H
Moulder
G
G
Maruyama
I N
IN
Barstead
R J
RJ
Rand
J B
JB
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D005091:Exons; D005260:Female; D005298:Fertility; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics*; D009154:Mutation; D009420:Nervous System / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D015183:Restriction Mapping; D017384:Sequence Deletion; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015801:Helminth Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C083141:phorbol ester binding protein