Patient-derived antibodies reveal the subcellular distribution and heterogeneous interactome of LGI1 - Archive ouverte HAL Access content directly
Journal Articles Brain - A Journal of Neurology Year : 2022

Patient-derived antibodies reveal the subcellular distribution and heterogeneous interactome of LGI1

Abstract

Autoantibodies against leucine-rich glioma-inactivated 1 occur in patients with encephalitis who present with frequent focal seizures and a pattern of amnesia consistent with focal hippocampal damage. To investigate whether the cellular and subcellular distribution of LGI1 may explain the localisation of these features, and hence gain broader insights into LGI1’s neurobiology, we analysed the detailed localisation of LGI1, and the diversity of its protein interactome, in mouse brains using patients-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/Kv1/MAGUK 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.
Fichier principal
Vignette du fichier
Ramirez-Franco.....EL FAR. 2022.pdf (159.69 Mo) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-03701887 , version 1 (08-09-2022)

Identifiers

Cite

Jorge Ramirez-Franco, Kévin Debreux, Johanna Extremet, Yves Maulet, Maya Belghazi, et al.. Patient-derived antibodies reveal the subcellular distribution and heterogeneous interactome of LGI1. Brain - A Journal of Neurology , 2022, pp.awac218. ⟨10.1093/brain/awac218⟩. ⟨hal-03701887⟩
186 View
82 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More