Presynaptic UNC-31 (CAPS) Is Required to Activate the Gαs Pathway of the Caenorhabditis elegans Synaptic Signaling Network
Abstract
C. elegans mutants lacking the dense-core vesicle priming protein UNC-31 (CAPS) share highly similar phenotypes with mutants lacking a neuronal Gαs pathway, including strong paralysis despite exhibiting near normal levels of steady-state acetylcholine release as indicated by drug sensitivity assays. Our genetic analysis shows that UNC-31 and neuronal Gαs are different parts of the same pathway and that the UNC-31/Gαs pathway is functionally distinct from the presynaptic Gαq pathway with which it interacts. UNC-31 acts upstream of Gαs because mutations that activate the Gαs pathway confer similar levels of strongly hyperactive, coordinated locomotion in both unc-31 null and (+) backgrounds. Using cell-specific promoters, we show that both UNC-31 and the Gαs pathway function in cholinergic motor neurons to regulate locomotion rate. Using immunostaining we show that UNC-31 is often concentrated at or near active zones of cholinergic motor neuron synapses. Our data suggest that presynaptic UNC-31 activity, likely acting via dense-core vesicle exocytosis, is required to locally activate the neuronal Gαs pathway near synaptic active zones.
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Both unc-31 and rund-1 mutants can be suppressed by an activating mutation in the Gαs ortholog gsa-1.
“both unc-31 and rund-1 mutants can be suppressed by an activating mutation in the Gαs ortholog gsa-1”
From Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation (2014) · cites this paper as Charlie et al., 2006
The Results (p. 8) report that the activating gsa-1(ce81) mutation strongly rescues paralysis in unc-31 null mutants. Our copy does not report suppression of rund-1 mutants; a search for rund-1 found no matching passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCAPS mutations suppress activated Gαq alleles, suggesting the proteins act in a pathway.
“Mutations in CAPS suppress activated alleles of Gαq”
From Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation (2014) · cites this paper as Charlie et al., 2006
The Results (p. 8) report that an activated Gαq allele combined with a CAPS null mutation produced approximately wild-type locomotion rather than the activated allele’s hyperactive locomotion, supporting suppression of that phenotype. But the paper concludes that CAPS acts with Gαs in a pathway functionally distinct from Gαq (Abstract, p. 2; Figure 11, p. 17), not that CAPS and Gαq act in the same pathway. (LLM, conf=0.88)
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Impaired dense core vesicle maturation in <i>Caenorhabditis elegans</i> mutants lacking Rab2
Edwards, S. L., Charlie, N. K., Richmond, J. E., Hegermann, J., Eimer, S., & Miller, K. G. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200902095 · Cited by 83 · see citing works
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- Authors
- Charlie, N. K., Schade, M. A., Thomure, A. M., & Miller, K. G.
- Affiliations
- Oklahoma Medical Research Foundation (US)
- Corresponding author
- Miller, Kenneth G
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02-01
- Volume
- 172
- Issue
- 2
- Pages
- 943-961
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2143364407
- Cited by
- 98
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 8 · 2012: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH062400, MH62400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- unc-31, CAPS, presynaptic signaling, synaptic vesicle exocytosis, cholinergic motor neurons, acetylcholine release, active zone, Caenorhabditis elegans
- MeSH terms
- Aldicarb, Animals, Calcium-Binding Proteins, Cholinesterase Inhibitors, Exocytosis, Muscles, Mutation, Neurons, Phenotype, Receptors, Cholinergic, Caenorhabditis elegans, Presynaptic Terminals, GTP-Binding Protein alpha Subunits, Gs, Caenorhabditis elegans Proteins
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