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Although pathological roles of MGAT3 and bisecting GlcNAc have been demonstrated in Alzheimer\u2019s disease, their physiological functions in neurons remain unclear. To identify their physiological functions, here we examine the morphology of neurons in knockout (Mgat3\u2212\/\u2212) mouse brains and investigate the expression and localization of bisecting GlcNAc-bearing glycoproteins involved in neuronal activity and morphogenesis. We found impaired neurite extension and spine maturation in cultured cortical neurons of Mgat3\u2212\/\u2212 mice, along with reduced stimulus-induced in vivo neuronal activity. Moreover, key glycoproteins for these processes (specifically \u03b1-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA]-type glutamate receptors) showed reduced accumulation in postsynaptic density membrane fractions and a weakened interaction with transmembrane AMPA receptor regulatory protein 8 in Mgat3\u2212\/\u2212 mouse brain. These results suggest that bisecting GlcNAc plays important roles in synaptic maturation, highlighting a new mechanism for neuronal activity regulated by specific N-glycans.<\/jats:p>","DOI":"10.1042\/bcj20260379","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:33:51Z","timestamp":1787837631000},"page":"1877-1890","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bisecting GlcNAc in\n                    <i>N<\/i>\n                    -glycan regulates synaptic maturation"],"prefix":"10.1042","volume":"483","author":[{"given":"Yuta","family":"Hashimoto","sequence":"first","affiliation":[{"name":"1Graduate School of Natural Science and Technology, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxue","family":"Bao","sequence":"additional","affiliation":[{"name":"2Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"3Department of Morphological Neuroscience, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan"},{"name":"4Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Watanave","sequence":"additional","affiliation":[{"name":"3Department of Morphological Neuroscience, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misuzu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"4Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, 501-1194, Japan"},{"name":"5Laboratory of Biological Chemistry, Faculty of Applied Biological Sciences, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Ohno","sequence":"additional","affiliation":[{"name":"6Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"6Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"2Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Tokoro","sequence":"additional","affiliation":[{"name":"2Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3181-9743","authenticated-orcid":false,"given":"Yasuhiko","family":"Kizuka","sequence":"additional","affiliation":[{"name":"1Graduate School of Natural Science and Technology, Gifu University, Gifu 501-1193, Japan"},{"name":"2Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"2026090304464481400_B1","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1038\/s41580-020-00294-x","article-title":"Global view of human protein glycosylation pathways and functions","volume":"21","author":"Schjoldager","year":"2020","journal-title":"Nat. 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