{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:47:07Z","timestamp":1790290027133,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acetylcholine (ACh) receptors (AChR) regulate neural circuit activity in multiple contexts. In humans, mutations in ionotropic acetylcholine receptor (iAChR) genes can cause neurological disorders, including myasthenia gravis and epilepsy. In Caenorhabditis elegans, iAChRs play multiple roles in the locomotor circuit. The cholinergic motor neurons express an ACR-2-containing pentameric AChR (ACR-2R) comprised of ACR-2, ACR-3, ACR-12, UNC-38, and UNC-63 subunits. A gain-of-function mutation in the non-\u03b1 subunit gene acr-2 [acr-2(gf)] causes defective locomotion as well as spontaneous convulsions. Previous studies of genetic suppressors of acr-2(gf) have provided insights into ACR-2R composition and assembly. Here, to further understand how the ACR-2R regulates neuronal activity, we expanded the suppressor screen for acr-2(gf)-induced convulsions. The majority of these suppressor mutations affect genes that play critical roles in synaptic transmission, including two novel mutations in the vesicular ACh transporter unc-17. In addition, we identified a role for a conserved major facilitator superfamily domain (MFSD) protein, mfsd-6, in regulating neural circuit activity. We further defined a role for the sphingosine (SPH) kinase (Sphk) sphk-1 in cholinergic neuron activity, independent of previously known signaling pathways. Overall, the genes identified in our study suggest that optimal modulation of synaptic activity is balanced by the differential activities of multiple pathways, and the novel alleles provide valuable reagents to further dissect neuronal mechanisms regulating the locomotor circuit.<\/jats:p>","DOI":"10.1534\/g3.117.042598","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T01:20:21Z","timestamp":1493860821000},"page":"2055-2063","source":"Crossref","is-referenced-by-count":20,"title":["Novel Mutations in Synaptic Transmission Genes Suppress Neuronal Hyperexcitation in<i>Caenorhabditis elegans<\/i>"],"prefix":"10.1093","volume":"7","author":[{"given":"Katherine A","family":"McCulloch","sequence":"first","affiliation":[{"name":"Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchuan B","family":"Qi","sequence":"additional","affiliation":[{"name":"Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seika","family":"Takayanagi-Kiya","sequence":"additional","affiliation":[{"name":"Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishi","family":"Jin","sequence":"additional","affiliation":[{"name":"Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093"},{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093"},{"name":"Howard Hughes Medical Institute, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Salvatore J","family":"Cherra","sequence":"additional","affiliation":[{"name":"Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2021042013014037700_bib1","doi-asserted-by":"crossref","first-page":"W3","DOI":"10.1093\/nar\/gkw343","article-title":"The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update.","volume":"44","author":"Afgan","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021042013014037700_bib2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1152\/physrev.00015.2008","article-title":"Mammalian nicotinic acetylcholine receptors: from structure to function.","volume":"89","author":"Albuquerque","year":"2009","journal-title":"Physiol. 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