Trans-synaptic LGI1-ADAM22-MAGUK in AMPA and NMDA receptor regulation

NEUROPHARMACOLOGY

卷:194

Article

Fukata, Yuko^1,2  Hirano, Yoko^1,3  Miyazaki, Yuri^1,2  Yokoi, Norihiko^1,2  Fukata, Masaki^1,2 

[1] Natl Inst Physiol Sci, Natl Inst Nat Sci, Dept Mol & Cellular Physiol, Div Membrane Physiol, Okazaki, Aichi 4448787, Japan

[2] SOKENDAI Grad Univ Adv Studies, Sch Life Sci, Dept Physiol Sci, Okazaki, Aichi 4448585, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Pediat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan

关键词: LGI1;    ADAM22;    MAGUK;    AMPA receptor;    NMDA receptor;    Synapse;    Epilepsy;    Limbic encephalitis;    Trans-synaptic nanocolumn;   

DOI  :  10.1016/j.neuropharm.2021.108628

来源: Elsevier

【 摘 要 】

Exquisitely-regulated synaptic transmission and plasticity underlie higher brain functions such as learning and memory. PSD-95, a member of the MAGUK family, scaffolds an array of postsynaptic proteins including AMPA and NMDA receptors, and plays essential roles in excitatory synaptic transmission and postsynaptic organization. Epilepsy-related secreted protein LGI1 and its receptor ADAM22 represent major constituent elements of the PSD-95-containing synaptic protein complex in the brain. Recent studies begin to reveal a trans-synaptic configuration of the LGI1-ADAM22 complex and its pivotal role in AMPA and NMDA receptor-mediated synaptic transmission through regulating MAGUKs. Especially interesting is that without the association with LGI1-ADAM22, PSD-95 cannot potentiate AMPA receptor-mediated synaptic transmission. Here, we review roles of LGI1-ADAM22 in synaptic function, and discuss its modes of action on the MAGUK regulation: as (i) a transsynaptic hub, (ii) an extracellular scaffold, and (iii) an allosteric activator. We also highlight patho-physiological roles of the LGI1-ADAM22-MAGUK linkage in synaptic disorders such as epilepsy and autoimmune limbic encephalitis.

【 授权许可】

Free