Disease relevance of unc-13

• Using pBT7, part of the Caenorhabditis elegans unc-13 gene product has been overproduced at a high level, approaching 50% of total Escherichia coli protein [1].

Psychiatry related information on unc-13

• The present study reports the identification by differential display PCR of Munc13-3, a mammalian homolog of the Caenorhabditis elegans "uncoordinated" gene (unc-13), as a candidate gene for critical-period neuronal plasticity, the expression of which is regulated according to this criterion specifically in visual cortex and not in frontal cortex [2].

High impact information on unc-13

• However, the number of synaptic vesicles at neuromuscular junctions was two- to threefold greater in unc-13 mutants than in wild-type animals [3].
• Mutants of unc-13 had normal nervous system architecture, and the densities of synapses and postsynaptic receptors were normal at the neuromuscular junction [3].
• Even when priming was restored, synaptic transmission remained defective in unc-13 mutants, suggesting that UNC-13 is also required for other aspects of secretion [4].
• These findings confirm that the unc-13 gene product has binding sites similar to those of protein kinase C and may be a component of an alternative transduction pathway of the diacylglycerol signal to a different effector function in the nervous system [5].
• In order to evaluate the function of the individual members of this multigene family, we sought to recover amber (UAG)-suppressing mutations from reversion experiments with animals carrying amber mutations in a nervous system-affecting gene (unc-13) or a sex-determining gene (tra-3) [6].

Biological context of unc-13

• We have analyzed the sequence alterations, immunostaining patterns, and behavioral phenotypes of 31 independent unc-13 alleles [7].
• We have identified a set of transcripts from the unc-13 locus in C. elegans resulting from alternative splicing and apparent alternative promoters [7].
• The fraction of essential genes that present relatively large targets for EMS was highest within the central cluster (dpy-5 to unc-13) [8].
• This suggests a crucial role for the unc-13 gene product in the mediation or regulation of synaptic vesicle exocytosis [9].
• More than 30 independent suppressor mutations have been obtained in the nematode C. elegans through reversion analysis of two unc-13 mutants [10].

Anatomical context of unc-13

• Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction [11].
• Our data suggest that the function of unc-13 in C. elegans is conserved in mammals and that Munc13s act as plasma membrane proteins in nerve terminals [12].

Associations of unc-13 with chemical compounds

• Recombination frequency increased approximately twofold across the dpy-5-unc-13 interval after treatment with 2000 rads (1 rad = 10 mGy) of cobalt 60 gamma radiation [13].
• A truncated protein containing the Munc homology domains (MHD1 and MHD2) and the carboxy-terminal C2 domain partially rescued both the behavioral and secretion defects of unc-13 mutants in C. elegans [14].
• Double mutants defective in both unc-13 and other genes involved in synaptic transmission showed the Unc-13 phenotype, rather than other mutant phenotypes, in terms of locomotion as well as of acetylcholine accumulation [15].

Other interactions of unc-13

• 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 [16].
• Importantly, analysis with unc-13 mutants indicates that sir-2.1 and daf-16 have overlapping and distinct roles in life span regulation [17].
• The unc-13 gene was expressed in most, if not all, neurons when analyzed by using chimeric constructs consisting of the unc-13 promoter and green fluorescence protein or beta-galactosidase reporter gene [15].
• Two genes, unc-15 and unc-13, are only 0.025 map units apart [18].

Analytical, diagnostic and therapeutic context of unc-13

• Most importantly, evoked release at both GABAergic and cholinergic synapses was almost absent in unc-13 null alleles, as determined by whole-cell, voltage-clamp techniques [3].
• Molecular cloning revealed that three homologues of unc-13 called Munc13-1, -13-2, and -13-3 are expressed in rat brain [12].

References