{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:45:42Z","timestamp":1791917142414,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012255","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000}}],"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM150658"],"award-info":[{"award-number":["R35GM150658"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL131403"],"award-info":[{"award-number":["R01HL131403"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS081320"],"award-info":[{"award-number":["R01NS081320"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001391","name":"Whitehall Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001395","name":"Wisconsin Alumni Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001395","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24PRE1188958"],"award-info":[{"award-number":["24PRE1188958"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    KCNH voltage-gated potassium channels regulate neuronal excitability, yet how their hallmark cyclic nucleotide-binding homology domains (CNBHDs) influence channel gating to regulate behavior remains unclear. Using an unbiased forward genetic screen in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , we identified a gain-of-function mutation in the EAG-subfamily KCNH channel EGL-2 that suppresses sleep. The mutation (G574E) alters a highly conserved glycine residue at the interface between CNBHDs of adjacent channel subunits. EGL-2 functions cell-autonomously in the central sleep-promoting neuron ALA.\n                    <jats:italic>In vivo<\/jats:italic>\n                    calcium imaging showed that the gain-of-function mutation suppresses sleep by inhibiting ALA neuronal activity, consistent with enhanced potassium channel activity. Genetic analysis demonstrated that the sleep-suppressing phenotype of G574E requires both an intact potassium selectivity filter and the intrinsic ligand-occupied CNBHD. A second substitution at the same glycine (G574R), which introduces a positively charged side chain in contrast to the negatively charged side chain in G574E, similarly suppresses sleep, indicating that perturbation of the CNBHD-CNBHD interface, rather than the specific amino acid change, underlies the phenotype. Moreover, mutations at the corresponding residue in the ERG-subfamily KCNH channels\n                    <jats:italic>C. elegans<\/jats:italic>\n                    UNC-103 and human hERG also produce gain-of-function effects, and electrophysiological analysis showed that hERG(G749R) shifts voltage-dependent channel activation to more negative potentials and accelerates activation kinetics. These findings identify EGL-2 as an important sleep regulator and uncover a conserved gating mechanism by which the intersubunit CNBHD-CNBHD interface restrains KCNH channel activation to regulate neuronal excitability and behavior.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012255","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:46:36Z","timestamp":1790876796000},"page":"e1012255","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Forward genetics reveals a conserved CNBHD-CNBHD interface that restrains EAG channel activation to regulate sleep"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9618-3910","authenticated-orcid":true,"given":"Xinyu","family":"Huang","sequence":"first","affiliation":[{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Department of Biology"]},{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Genetics Training Program"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudharsan","family":"Kannan","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Department of Neuroscience, School of Medicine and Public Health"]},{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Neuroscience Training Program, School of Medicine and Public Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail A.","family":"Robertson","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Department of Neuroscience, School of Medicine and Public Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-5762","authenticated-orcid":true,"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison","place":["Madison, Wisconsin, United States of America"],"department":["Department of Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"8","key":"pgen.1012255.ref001","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1073\/pnas.91.8.3438","article-title":"A family of potassium channel genes related to eag in Drosophila and mammals","volume":"91","author":"JW Warmke","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1012255.ref002","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/j.1749-6632.1999.tb11297.x","article-title":"The eag family of K+ channels in Drosophila and mammals","volume":"868","author":"B Ganetzky","year":"1999","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"pgen.1012255.ref003","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1113\/JP275477","article-title":"Ether-\u00e0-go-go K+ channels: Effective modulators of neuronal excitability","volume":"596","author":"CK Bauer","year":"2018","journal-title":"J Physiol"},{"issue":"6300","key":"pgen.1012255.ref004","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1126\/science.aaf8070","article-title":"Structure of the voltage-gated K\u207a channel Eag1 reveals an alternative voltage sensing mechanism","volume":"353","author":"JR Whicher","year":"2016","journal-title":"Science"},{"issue":"3","key":"pgen.1012255.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2017.03.048","article-title":"Cryo-EM structure of the open human ether-\u00e0-go-go-Related K+ channel hERG","volume":"169","author":"W 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He","year":"2019","journal-title":"Genetics"},{"issue":"7458","key":"pgen.1012255.ref030","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature12354","article-title":"Ultrasensitive fluorescent proteins for imaging neuronal activity","volume":"499","author":"T-W Chen","year":"2013","journal-title":"Nature"},{"issue":"11","key":"pgen.1012255.ref031","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1534\/g3.118.200662","article-title":"An efficient genome editing strategy to generate putative null mutants in Caenorhabditis elegans using CRISPR\/Cas9","volume":"8","author":"H Wang","year":"2018","journal-title":"G3 (Bethesda)"},{"issue":"4","key":"pgen.1012255.ref032","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/S0006-3495(94)80887-2","article-title":"Mutations in the K+ channel signature sequence","volume":"66","author":"L Heginbotham","year":"1994","journal-title":"Biophys 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A re-examination","volume":"36","author":"JW Moore","year":"1981","journal-title":"Biophys J"},{"issue":"7","key":"pgen.1012255.ref054","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/0028-3908(96)00113-X","article-title":"Potassium currents expressed from Drosophila and mouse eag cDNAs in Xenopus oocytes","volume":"35","author":"GA Robertson","year":"1996","journal-title":"Neuropharmacology"},{"issue":"19","key":"pgen.1012255.ref055","doi-asserted-by":"crossref","first-page":"4451","DOI":"10.1002\/j.1460-2075.1994.tb06767.x","article-title":"Functional expression of a rat homologue of the voltage gated either \u00e1 go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart","volume":"13","author":"J Ludwig","year":"1994","journal-title":"EMBO 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