{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:45:49Z","timestamp":1760150749640,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23K08620"],"award-info":[{"award-number":["23K08620"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in multiple epidermal growth factor-like domain 8 (MEGF8), a multidomain transmembrane protein encoded by a gene conserved across species, cause Carpenter\u2019s syndrome, which is associated with learning disabilities, mental health issues, and left\u2013right patterning abnormalities. MEGF8 interacts with MGRN1, a protein that functions as an E3 ubiquitin ligase and is involved in multiple physiological and pathological processes. However, the mechanism underlying the distribution of MEGF8 in the central nervous system (CNS) and its cellular and subcellular locations remain unknown. This study aimed to map MEGF8 in the mouse CNS using a new antibody. We discovered that MEGF8 was distributed in the majority of neuronal cell somata across most CNS regions. High levels of MEGF8 were expressed in the neuropils of the CNS gray matter. Immunoelectron microscopy showed that MEGF8 was present in the synapses and around the outer mitochondrial membrane. These findings show that MEGF8 is uniformly distributed throughout the mouse CNS, and its distribution indicates that it plays a substantial role in synaptic and mitochondrial functions. To the best of our knowledge, this is the first study to document MEGF8 distribution in the CNS.<\/jats:p>","DOI":"10.3390\/cells13010063","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T09:56:27Z","timestamp":1703757387000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunohistochemical and Immunoelectron Microscopical Distribution of MEGF8 in the Mouse Central Nervous System"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-7167","authenticated-orcid":false,"given":"Kazuhiko","family":"Nakadate","sequence":"first","affiliation":[{"name":"Department of Basic Science, Educational and Research Center for Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoharu","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Basic Science, Educational and Research Center for Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.ajhg.2012.08.027","article-title":"Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization","volume":"91","author":"Twigg","year":"2012","journal-title":"Am. 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