薬理学講座の鈴木です。
11月6日のNCでは下記の論文をご紹介します。
Kainate receptors regulate synaptic integrity and plasticity by forming
a complex with synaptic organizers in the cerebellum.
Cell Reports, 2024, 43, 114427
Kakegawa et al
Highlights
•Kainate receptors (KARs) are expressed at climbing fiber (CF)-Purkinje
cell (PC) synapses
•KARs regulate CF-PC synaptic integrity, plasticity, and motor learning
•KARs bind C1ql1 via the amino-terminal domain to stabilize C1ql1 and
Bai3 at synapses
•KARs stabilize synapses as a scaffold, independent of ionotropic or
metabotropic functions
Summary
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.