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To investigate whether the cellular and subcellular distribution of LGI1 may explain the localization of these features, and hence gain broader insights into LGI1\u2019s neurobiology, we analysed the detailed localization of LGI1 and the diversity of its protein interactome, in mouse brains using patient-derived recombinant monoclonal LGI1 antibodies. Combined immunofluorescence and mass spectrometry analyses showed that LGI1 is enriched in excitatory and inhibitory synaptic contact sites, most densely within CA3 regions of the hippocampus. LGI1 is secreted in both neuronal somatodendritic and axonal compartments, and occurs in oligodendrocytic, neuro-oligodendrocytic and astro-microglial protein complexes. Proteomic data support the presence of LGI1\u2013Kv1\u2013MAGUK complexes, but did not reveal LGI1 complexes with postsynaptic glutamate receptors. Our results extend our understanding of regional, cellular and subcellular LGI1 expression profiles and reveal novel LGI1-associated complexes, thus providing insights into the complex biology of LGI1 and its relationship to seizures and memory loss.<\/jats:p>","DOI":"10.1093\/brain\/awac218","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T14:36:06Z","timestamp":1655822166000},"page":"3843-3858","source":"Crossref","is-referenced-by-count":27,"title":["Patient-derived antibodies reveal the subcellular distribution and heterogeneous interactome of LGI1"],"prefix":"10.1093","volume":"145","author":[{"given":"Jorge","family":"Ramirez-Franco","sequence":"first","affiliation":[{"name":"INSERM, Aix-Marseille Universit\u00e9 (AMU), UMR 1072, Unit\u00e9 de Neurobiologie des canaux Ioniques et de la Synapse , 13015 Marseille , 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Marchot","sequence":"additional","affiliation":[{"name":"Laboratoire \u2018Architecture et Fonction des Macromol\u00e9cules Biologiques (AFMB)\u2019, CNRS, Aix-Marseille Universit\u00e9 , 13288 cedex 09 Marseille , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Paneva","sequence":"additional","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford , Oxford , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Debanne","sequence":"additional","affiliation":[{"name":"INSERM, Aix-Marseille Universit\u00e9 (AMU), UMR 1072, Unit\u00e9 de Neurobiologie des canaux Ioniques et de la Synapse , 13015 Marseille , 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