%0 Journal Article
%T Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum.
%A Kakegawa W
%A Paternain AV
%A Matsuda K
%A Aller MI
%A Iida I
%A Miura E
%A Nozawa K
%A Yamasaki T
%A Sakimura K
%A Yuzaki M
%A Lerma J
%J Cell Rep
%V 43
%N 7
%D 2024 Jul 23
%M 38986610
暂无%R 10.1016/j.celrep.2024.114427
%X Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum.