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Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity

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Item Type:Article
Title:Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity
Creators Name:Miyazaki, Y. and Otsuka, T. and Yamagata, Y. and Endo, T. and Sanbo, M. and Sano, H. and Kobayashi, K. and Inahashi, H. and Kornau, H.C. and Schmitz, D. and Prüss, H. and Meijer, D. and Hirabayashi, M. and Fukata, Y. and Fukata, M.
Abstract:Neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism, involve altered synaptic transmission and plasticity. Functional characterization of their associated genes is vital for understanding physio-pathological brain functions. LGI3 is a recently recognized ID-associated gene encoding a secretory protein related to an epilepsy-gene product, LGI1. Here, we find that LGI3 is uniquely secreted from oligodendrocytes in the brain and enriched at juxtaparanodes of myelinated axons, forming nanoscale subclusters. Proteomic analysis using epitope-tagged Lgi3 knockin mice shows that LGI3 uses ADAM23 as a receptor and selectively co-assembles with Kv1 channels. A lack of Lgi3 in mice disrupts juxtaparanodal clustering of ADAM23 and Kv1 channels and suppresses Kv1-channel-mediated short-term synaptic plasticity. Collectively, this study identifies an extracellular organizer of juxtaparanodal Kv1 channel clustering for finely tuned synaptic transmission. Given the defective secretion of the LGI3 missense variant, we propose a molecular pathway, the juxtaparanodal LGI3-ADAM23-Kv1 channel, for understanding neurodevelopmental disorders.
Keywords:LGI3, ADAM23, Kv1 Channel, Juxtaparanode, Oligodendrocyte, Short-Term Synaptic Plasticity, Intellectual Disability, Nanocluster, STED, Neurodevelopmental Disorders, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:113634
Date:23 January 2024
Official Publication:https://doi.org/10.1016/j.celrep.2023.113634
PubMed:View item in PubMed

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