{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:54Z","timestamp":1772118774257,"version":"3.50.1"},"reference-count":54,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009622","name":"Stichting Zeldzame Ziekten Fonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    North Sea Progressive Myoclonus Epilepsy (NS\u2010PME) is a rare genetic disease that presents at an early age with progressive ataxia, myoclonus, and epilepsy. The disease is caused by a mutation in the Golgi SNAP receptor 2 gene (GOSR2). However, the consequences of this genetic defect at the cellular level are still unknown. Using a NS\u2010PME\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    <\/jats:styled-content>\n                    model, it was previously found that knockdown of\n                    <jats:italic>membrin<\/jats:italic>\n                    , the fruit fly GOSR2 ortholog, in glial cells leads to progressive heat\u2010induced seizure\u2010like behavior in adult flies. Upon close inspection, we found NS\u2010PME flies not only show progressive heat\u2010induced seizures but also disrupted sleep architecture (higher number of shorter sleep bouts). Here we asked what glial cellular consequences could be underlying these phenotypes of\n                    <jats:italic>membrin<\/jats:italic>\n                    knockdown. First, we investigate whether these phenotypes are attributed to specific glial types; we found that these phenotypes were partly reproduced with specific knockdown of\n                    <jats:italic>membrin<\/jats:italic>\n                    in perineurial glia only. Next, we show that Innexin2, a gap junction protein specifically expressed in glia, is affected upon\n                    <jats:italic>membrin<\/jats:italic>\n                    knockdown, with an altered expression pattern and reduced protein levels. Finally, glial overexpression of Innexin2 in the background of glial\n                    <jats:italic>membrin<\/jats:italic>\n                    knockdown strongly ameliorates the heat\u2010induced seizure phenotype, disrupted sleep architecture, as well as Innexin2 expression pattern, corroborating the importance of Innexin2 in maintaining neuronal homeostasis in NS\u2010PME. These findings show that dysregulation of Innexin2 at least partially underlies the phenotypes of\n                    <jats:italic>membrin<\/jats:italic>\n                    knockdown in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    <\/jats:styled-content>\n                    and could suggest a similar role of Innexin2\u2010like proteins in the human disease NS\u2010PME.\n                  <\/jats:p>","DOI":"10.1002\/jnr.70087","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T10:18:48Z","timestamp":1762769928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of Glial Gap Junction Protein Innexin2 Mediates Seizures and Disrupted Sleep in a\n                    <i>Drosophila<\/i>\n                    Model for North Sea Progressive Myoclonus Epilepsy"],"prefix":"10.1002","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7106-4325","authenticated-orcid":false,"given":"Nicola A.","family":"Grzeschik","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences European Research Institute for the Biology of Ageing University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-8344","authenticated-orcid":false,"given":"Roald A.","family":"Lambrechts","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center Groningen, University of Groningen  Groningen the Netherlands"},{"name":"Expertise Center Movement Disorders Groningen University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3695-1305","authenticated-orcid":false,"given":"Marianne","family":"van der Zwaag","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences European Research Institute for the Biology of Ageing University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4130-3775","authenticated-orcid":false,"given":"Ellie","family":"Eggens\u2010Meijer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences European Research Institute for the Biology of Ageing University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-6063","authenticated-orcid":false,"given":"Ody C. M.","family":"Sibon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences European Research Institute for the Biology of Ageing University Medical Center Groningen, University of Groningen  Groningen the Netherlands"},{"name":"Expertise Center Movement Disorders Groningen University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-223X","authenticated-orcid":false,"given":"Jenke A.","family":"Gorter","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences European Research Institute for the Biology of Ageing University Medical Center Groningen, University of Groningen  Groningen the Netherlands"},{"name":"Expertise Center Movement Disorders Groningen University Medical Center Groningen, University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CUB.2022.03.040"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43326"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.10.017"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2005.02.013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2017.05.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22737"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.10.012"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt021"},{"issue":"2","key":"e_1_2_10_10_1","first-page":"15","article-title":"Targeted Gene Expression as a Means of Altering Cell Fates and Generating Dominant Phenotypes","volume":"118","author":"Brand A. 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