ArticleGenetics2005
Mutations that rescue the paralysis of Caenorhabditis elegans ric-8 (synembryn) mutants activate the G alpha(s) pathway and define a third major branch of the synaptic signaling network.
Article in Genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed.
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- Cell non-autonomous signaling through the conserved C. elegans glycoprotein hormone receptor FSHR-1 regulates cholinergic neurotransmission.PLoS genetics · 2024Article
- Opposing action of the FLR-2 glycoprotein hormone and DRL-1/FLR-4 MAP kinases balance p38-mediated growth and lipid homeostasis in C. elegans.PLoS biology · 2023Article
- Patient-specific variants of NFU1/NFU-1 disrupt cholinergic signaling in a model of multiple mitochondrial dysfunctions syndrome 1.Disease models & mechanisms · 2023Article
- GPCR signaling regulates severe stress-induced organismic death in Caenorhabditis elegans.Aging cell · 2023Article
- A metazoan-specific C-terminal motif in EXC-4 and Gα-Rho/Rac signaling regulate cell outgrowth during tubulogenesis in C. elegans.Development (Cambridge, England) · 2022Article
- A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.Cell reports · 2022Article
- Functional Insights into Protein Kinase A (PKA) Signaling fromLife (Basel, Switzerland) · 2022Review
- Dopamine D1- and D2-like receptors oppositely regulate lifespan via a dietary restriction mechanism in Caenorhabditis elegans.BMC biology · 2022Article
- A glial ClC ClNeuron · 2022Article
- Reduced CaFrontiers in neuroscience · 2022Article
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- Gα/GSA-1 works upstream of PKA/KIN-1 to regulate calcium signaling and contractility in the Caenorhabditis elegans spermatheca.PLoS genetics · 2020Article
- The Enigmatic Canal-Associated Neurons RegulateGenetics · 2019Article
- Article
- Neurotransmitter signaling through heterotrimeric G proteins: insights from studies in C. elegans.WormBook : the online review of C. elegans biology · 2018Review
- Sentryn Acts with a Subset of Active Zone Proteins To Optimize the Localization of Synaptic Vesicles inGenetics · 2018Article
- Sentryn and SAD Kinase Link the Guided Transport and Capture of Dense Core Vesicles inGenetics · 2018Article
19 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
To identify hypothesized missing components of the synaptic G alpha(o)-G alpha(q) signaling network, which tightly regulates neurotransmitter release, we undertook two large forward genetic screens in the model organism C. elegans and focused first on mutations that strongly rescue the paralysis of ric-8(md303) reduction-of-function mutants, previously shown to be defective in G alpha(q) pathway activation. Through high-resolution mapping followed by sequence analysis, we show that these mutations affect four genes. Two activate the G alpha(q) pathway through gain-of-function mutations in G alpha(q); however, all of the remaining mutations activate components of the G alpha(s) pathway, including G alpha(s), adenylyl cyclase, and protein kinase A. Pharmacological assays suggest that the G alpha(s) pathway-activating mutations increase steady-state neurotransmitter release, and the strongly impaired neurotransmitter release of ric-8(md303) mutants is rescued to greater than wild-type levels by the strongest G alpha(s) pathway activating mutations. Using transgene induction studies, we show that activating the G alpha(s) pathway in adult animals rapidly induces hyperactive locomotion and rapidly rescues the paralysis of the ric-8 mutant. Using cell-specific promoters we show that neuronal, but not muscle, G alpha(s) pathway activation is sufficient to rescue ric-8(md303)'s paralysis. Our results appear to link RIC-8 (synembryn) and a third major G alpha pathway, the G alpha(s) pathway, with the previously discovered G alpha(o) and G alpha(q) pathways of the synaptic signaling network.
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