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A Murine Neural-Specific Homolog Corrects Cholinergic Defects inCaenorhabditis elegans unc-18Mutants
- Source :
- The Journal of Neuroscience. 16:6695-6702
- Publication Year :
- 1996
- Publisher :
- Society for Neuroscience, 1996.
-
Abstract
- Caenorhabditis elegansUNC-18 protein, homologous to yeast Sec1p, is important in neurotransmitter release, because theunc-18mutation leads to severe paralysis and presynaptic acetylcholine (ACh) accumulation. To examine the functional conservation in mammals, we tried to isolateunc-18isoforms 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 transgenicunc-18mutants to test biological activity of mouse Munc-18-1 and Munc-18-3 under the control ofC. elegans unc-18promoter. Munc-18-1 compensates for severe locomotion disability and cholinergic defects, e.g., abnormal sensitivities to cholinesterase inhibitors and cholinergic receptor agonists inunc-18mutants, but Munc-18-3 fails. These data suggest that Munc-18-1 andC. elegans unc-18may play positive roles in ACh release and that the molecular mechanism of neuronal regulated secretion has been partially conserved from nematodes to mammals.
- Subjects :
- Transgene
Molecular Sequence Data
Vesicular Transport Proteins
Nerve Tissue Proteins
medicine.disease_cause
Animals, Genetically Modified
Mice
Munc18 Proteins
Antibody Specificity
medicine
Animals
Humans
RNA, Messenger
Cloning, Molecular
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Gene
Peptide sequence
gamma-Aminobutyric Acid
Acetylcholine receptor
Genetics
Neurotransmitter Agents
Mutation
Base Sequence
Sequence Homology, Amino Acid
biology
cDNA library
General Neuroscience
Genetic Complementation Test
Helminth Proteins
Articles
Phosphoproteins
biology.organism_classification
Cholinergic Fibers
Cholinergic
Synaptic Vesicles
Carrier Proteins
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....34384ca54b243c41e0d83e4f35ebfba1