| First Author | Gengyo-Ando K | Year | 1996 |
| Journal | J Neurosci | Volume | 16 |
| Issue | 21 | Pages | 6695-702 |
| PubMed ID | 8824310 | Mgi Jnum | J:36075 |
| Mgi Id | MGI:83526 | Doi | 10.1523/JNEUROSCI.16-21-06695.1996 |
| Citation | Gengyo-Ando K, et al. (1996) A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. J Neurosci 16(21):6695-702 |
| abstractText | Caenorhabditis elegans UNC-18 protein, homologous to yeast Sec1p, is important in neurotransmitter release, because the unc-18 mutation leads to severe paralysis and presynaptic acetylcholine (ACh) accumulation. 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. Neural genes were identical to Munc-18 (also known as n-Sec1 or rbSec1), identified in rat and bovine brains as a syntaxin-binding protein. According to Munc-18 terminology, we call the neural genes Munc-18-1 and the ubiquitous genes Munc-18-3. These mammalian isoforms exhibit 58% (Munc-18-1) and 42-43% (Munc-18-3) amino acid sequence identity with UNC-18. Next, we constructed transgenic unc-18 mutants to test biological activity of mouse Munc-18-1 and Munc-18-3 under the control of C. elegans unc-18 promoter. Munc-18-1 compensates for severe locomotion disability and cholinergic defects, e.g., abnormal sensitivities to cholinesterase inhibitors and cholinergic receptor agonists in unc-18 mutants, but Munc-18-3 fails. These data suggest that Munc-18-1 and C. elegans unc-18 may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals. |
