Disease relevance of unc-18

• In gene expression, unc-64 closely resembles unc-18, that is, both are expressed in neural cells, especially in motor neurons and neurons constituting head ganglions [1].

High impact information on unc-18

• Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin [2].
• In C. elegans, unc-18 belongs to a group of genes defined by mutations with a paralytic phenotype and accumulations of acetylcholine, suggesting a defect in neurotransmitter release [2].
• The C. elegans unc-18 gene encodes a protein expressed in motor neurons [3].
• The C. elegans unc-18 gene is required to maintain normal acetylcholine levels [3].
• To examine the functional conservation in mammals, we tried to isolate unc-18 isoforms from mouse and human brain cDNA libraries and obtained two classes of isoforms-neural genes and ubiquitous genes [4].

Biological context of unc-18

• The unc-18 location within this region was determined by rescuing the unc-18 mutant phenotype in a germ-line transformation experiment and identifying transcripts affected by four independent unc-18 mutations [5].
• These results show that the unc-18 gene plays a role in development as well as in the kinetics of ACh metabolism [5].
• The Caenorhabditis elegans unc-13, unc-18, and unc-64 genes are required for normal synaptic transmission [6].
• We isolated an allele of unc-18, a previously reported member of the Sec1/Munc-18 (SM) family of proteins that is necessary for regulated exocytosis in C. elegans motor neurons [7].

Anatomical context of unc-18

• Defects in synaptic vesicle docking in unc-18 mutants [8].
• A cDNA clone encoding a human homolog of the Caenorhabditis elegans unc-18 gene was identified following random sequencing of clones from IL-2-activated human NK cells [9].
• We have screened the mouse cDNA library of an MIN6 cell line, derived from pancreatic beta cells, for its novel isoform and have identified a cDNA encoding a 593-amino acid protein having 63, 53, and 30% identity with munc-18/n-Sec1/rbSec1, Caenorhabditis elegans unc18, and Saccharomyces cerevisiae Sec1p, respectively [10].

Associations of unc-18 with chemical compounds

• The unc-18 gene encodes a novel protein affecting the kinetics of acetylcholine metabolism in the nematode Caenorhabditis elegans [5].

Other interactions of unc-18

• Alleles of dyf-2 and unc-13 were isolated, and mutants of unc-18, a gene that interacts with unc-13, were also found to be long lived [11].
• Here we describe the cloning, and the molecular and genetic characterization of the unc-64 gene, especially in relation to unc-18. unc-64 encodes a protein (C. elegans syntaxin) showing sequence and structural similarities to mammalian syntaxin 1A [1].

References