unc
 -
 1
 : A stomatin homologue controls sensitivity to volatile anesthetics in
 Caenorhabditis elegans

Rajaram, Shantadurga; Sedensky, Margaret M.; Morgan, Phil G.

doi:10.1073/pnas.95.15.8761

Cited by 72 publications

(59 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…unc-9 has strong genetic interactions with a second gene, unc-1, whose mutation leads to a similar uncoordinated and anesthesia-resistant phenotype (38). unc-1 encodes a stomatin-like integral membrane protein that colocalizes with UNC-9 proteins and modulates the gating of UNC-9 gap junctions in muscle ( Fig.…”

mentioning

confidence: 99%

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Jang

Levy

Flavell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.innexin | neural circuits | electrical synapses | stomatin | sensory behavior

show abstract

mentioning

confidence: 99%

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Jang

Levy

Flavell

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Three stomatin-like genes, unc-1, unc-24, and mec-2, are expressed in neurons (19 -21). Mutations in neuronal stomatin-like genes unc-1 and unc-24 alter sensitivity to volatile anesthetics (VAs) (21), linking stomatin function with a neuronal mechanism that has eluded description for 150 years. The current understanding of neuronal SLP function in C. elegans is limited to an association between SLPs and epithelial sodium channels (ENaCs) (7,22).…”

mentioning

confidence: 99%

“…Of the 10 SLPs in C. elegans, we studied unc-1 and unc-24 because of their abnormal locomotion and their ability to modify sensitivity to VAs as measured by immobility (11,21). By studying genetic modifiers of neuronal stomatin mutants, we hope to better understand the function of stomatin-like genes, VA action, and conserved neuronal mechanisms.…”

mentioning

confidence: 99%

Sulfated Signal from ASJ Sensory Neurons Modulates Stomatin-dependent Coordination in Caenorhabditis elegans

Carroll

Dubyak²,

Sedensky

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The neuronal stomatin-like proteins UNC-1 and UNC-24 play important roles in the nervous system of Caenorhabditis elegans. These neuronal stomatin-like proteins are putative chaperone proteins that can modify volatile anesthetic sensitivity and disrupt coordinated locomotion. A suppressor of unc-1 and unc-24, named ssu-1(fc73) (for suppressor of stomatin uncoordination), suppresses three phenotypes of neuronal stomatin-like protein deficiency as follows: volatile anesthetic sensitivity, uncoordinated locomotion, and a constitutive alternative developmental phenotype known as dauer. Here we provide the first phenotypic characterization of ssu-1, predicted to be the only C. elegans cytosolic alcohol sulfotransferase, a family of enzymes that catalyze a sulfate linkage with the alcohol group of small molecules for the purposes of detoxification or modification of signaling. In vitro enzyme analysis of bacterially expressed SSU-1 demonstrates sulfotransferase activity and thus confirms the function predicted by protein sequence similarities. Whereas unc-1 is expressed in the majority of neurons of C. elegans, expression of SSU-1 protein in only the two ASJ amphid interneurons is sufficient to restore the wild type phenotype. This work demonstrates that SSU-1 is a functional sulfotransferase that likely modifies endocrine signaling in C. elegans. The expression of SSU-1 in the ASJ neurons refines the understanding of the function of these cells and supports their classification as endocrine tissue. The relationship of unc-1, unc-24, and ssu-1 is the first association of neuronal stomatin-like proteins sharing regulatory roles with a sulfotransferase enzyme.

show abstract

“…Positional cloning of two of the loci has been accomplished. One gene is a mitochondrial protein, and the other is a stomatin (42)(43)(44). The role of the human orthologs in anesthetic action is under investigation.…”

mentioning

confidence: 99%

Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

Nägele

Metz

Crowder

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nitrous oxide (N2O, also known as laughing gas) and volatile anesthetics (VAs), the original and still most widely used general anesthetics, produce anesthesia by ill-defined mechanisms. Electrophysiological experiments in vertebrate neurons have suggested that N 2O and VAs may act by distinct mechanisms; N2O antagonizes the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, whereas VAs alter the function of a variety of other synaptic proteins. However, no genetic or pharmacological experiments have demonstrated that any of these in vitro actions are responsible for the behavioral effects of either class of anesthetics. By using genetic tools in Caenorhabditis elegans, we tested whether the action of N 2 O requires the NMDA receptor in vivo and whether its mechanism is shared by VAs. Distinct from the action of VAs, N 2O produced behavioral defects highly specific and characteristic of that produced by loss-of-function mutations in both NMDA and non-NMDA glutamate receptors. A null mutant of nmr-1, which encodes a C. elegans NMDA receptor, was completely resistant to the behavioral effects of N 2O, whereas a non-NMDA receptor-null mutant was normally sensitive. The N 2O-resistant nmr-1(null) mutant was not resistant to VAs. Likewise, VA-resistant mutants had wild-type sensitivity to N 2O. Thus, the behavioral effects of N 2O require the NMDA receptor NMR-1, consistent with the hypothesis formed from vertebrate electrophysiological data that a major target of N 2O is the NMDA receptor.

show abstract

unc - 1 : A stomatin homologue controls sensitivity to volatile anesthetics in Caenorhabditis elegans

Cited by 72 publications

References 36 publications

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Sulfated Signal from ASJ Sensory Neurons Modulates Stomatin-dependent Coordination in Caenorhabditis elegans

Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

Contact Info

Product

Resources

About

unc - 1 : A stomatin homologue controls sensitivity to volatile anesthetics in Caenorhabditis elegans

Cited by 72 publications

References 36 publications

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

Sulfated Signal from ASJ Sensory Neurons Modulates Stomatin-dependent Coordination in Caenorhabditis elegans

Nitrous oxide (N 2 O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans

Contact Info

Product

Resources

About

Nitrous oxide (N ₂ O) requires the N -methyl- d -aspartate receptor for its action in Caenorhabditis elegans