Document Detail


Resistance to volatile anesthetics by mutations enhancing excitatory neurotransmitter release in Caenorhabditis elegans.
MedLine Citation:
PMID:  15514057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular mechanisms whereby volatile general anesthetics (VAs) disrupt behavior remain undefined. In Caenorhabditis elegans mutations in the gene unc-64, which encodes the presynaptic protein syntaxin 1A, produce large allele-specific differences in VA sensitivity. UNC-64 syntaxin normally functions to mediate fusion of neurotransmitter vesicles with the presynaptic membrane. The precise role of syntaxin in the VA mechanism is as yet unclear, but a variety of results suggests that a protein interacting with syntaxin to regulate neurotransmitter release is essential for VA action in C. elegans. To identify additional proteins that function with syntaxin to control neurotransmitter release and VA action, we screened for suppressors of the phenotypes produced by unc-64 reduction of function. Loss-of-function mutations in slo-1, which encodes a Ca(2+)-activated K+ channel, and in unc-43, which encodes CaM-kinase II, and a gain-of-function mutation in egl-30, which encodes Gqalpha, were isolated as syntaxin suppressors. The slo-1 and egl-30 mutations conferred resistance to VAs, but unc-43 mutations did not. The effects of slo-1 and egl-30 on VA sensitivity can be explained by their actions upstream or parallel to syntaxin to increase the level of excitatory neurotransmitter release. These results strengthen the link between transmitter release and VA action.
Authors:
Ammar H Hawasli; Owais Saifee; Christine Liu; Michael L Nonet; C Michael Crowder
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genetics     Volume:  168     ISSN:  0016-6731     ISO Abbreviation:  Genetics     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-29     Completed Date:  2005-03-15     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  831-43     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Inhalation / pharmacology*
Animals
Antigens, Surface / genetics
Caenorhabditis elegans / genetics*,  metabolism
Caenorhabditis elegans Proteins / genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / deficiency,  genetics
Drug Resistance*
GTP-Binding Protein alpha Subunits, Gq-G11 / deficiency,  genetics
Large-Conductance Calcium-Activated Potassium Channels
Membrane Proteins / metabolism*
Mutation / genetics*
Nerve Tissue Proteins / deficiency,  genetics
Neurotransmitter Agents / metabolism*
Phenotype
Potassium Channels, Calcium-Activated / genetics,  metabolism
Qa-SNARE Proteins
Suppression, Genetic
Syntaxin 1
Grant Support
ID/Acronym/Agency:
R01 GM059781/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Antigens, Surface; 0/Caenorhabditis elegans Proteins; 0/Egl-30 protein, C elegans; 0/Large-Conductance Calcium-Activated Potassium Channels; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Neurotransmitter Agents; 0/Potassium Channels, Calcium-Activated; 0/Qa-SNARE Proteins; 0/Syntaxin 1; 0/slo-1 protein, C elegans; 0/unc-64 protein, C elegans; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 2.7.11.17/unc-43 protein, C elegans; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gq-G11
Comments/Corrections

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