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Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans

van Swinderen, Bruno and Metz, Laura B. and Shebester, Laynie D. and Mendel, Jane E. and Sternberg, Paul W. and Crowder, C. Michael (2001) Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans. Genetics, 158 (2). pp. 643-655. ISSN 0016-6731. PMCID PMC1461665. https://resolver.caltech.edu/CaltechAUTHORS:20190514-103243544

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Abstract

To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the α-subunit of Go, have EC_(50)s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goα, and presynaptic Goα-effectors are candidate VA molecular targets.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.genetics.org/content/158/2/643.longPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1461665PubMed CentralArticle
ORCID:
AuthorORCID
Sternberg, Paul W.0000-0002-7699-0173
Alternate Title:Goalpha regulates volatile anesthetic action in Caenorhabditis elegans
Additional Information:© 2001 by the Genetics Society of America. Manuscript received October 20, 2000; Accepted for publication March 7, 2001. We thank Yvonne Hajdu-Cronin and Shahla Gharib for technical assistance in sequencing goa-1(sy192) and Yvonne Hajdu-Cronin, Wen Chen, and Russell Roberson for communication of unpublished results. This work was supported by National Institutes of Health RO1 GM-55832-01 and RO1 GM-59781-02 (C.M.C.), the Foundation for Anesthesia Education and Research (C.M.C.). P.W.S. is an investigator of the Howard Hughes Medical Institute. Some of the C. elegans strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources.
Funders:
Funding AgencyGrant Number
NIHRO1 GM-55832-01
NIHRO1 GM-59781-02
Foundation for Anesthesia Education and ResearchUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC1461665
Record Number:CaltechAUTHORS:20190514-103243544
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190514-103243544
Official Citation:Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans. Bruno van Swinderen, Laura B. Metz, Laynie D. Shebester, Jane E. Mendel, Paul W. Sternberg and C. Michael Crowder. GENETICS June 1, 2001 vol. 158 no. 2 643-655
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95480
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:14 May 2019 20:53
Last Modified:03 Oct 2019 21:13

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