A kinesin 1-protrudin complex mediates AMPA receptor synaptic removal during long-term depression
Cell Reports. 2021-08-01; 36(5): 109499
DOI: 10.1016/j.celrep.2021.109499
Brachet A(1), Lario A(2), Fernández-Rodrigo A(2), Heisler FF(3), Gutiérrez Y(2),
Lobo C(2), Kneussel M(3), Esteban JA(4).
Author information:
(1)Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de
Madrid, 28049 Madrid, Spain. Electronic address: .
(2)Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de
Madrid, 28049 Madrid, Spain.
(3)Center for Molecular Neurobiology (ZMNH), University Medical Center
Hamburg-Eppendorf (UKE), D-20251 Hamburg, Germany.
(4)Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de
Madrid, 28049 Madrid, Spain. Electronic address: .
The synaptic removal of AMPA-type glutamate receptors (AMPARs) is a core
mechanism for hippocampal long-term depression (LTD). In this study, we address
the role of microtubule-dependent transport of AMPARs as a driver for vesicular
trafficking and sorting during LTD. Here, we show that the kinesin-1 motor
KIF5A/C is strictly required for LTD expression in CA3-to-CA1 hippocampal
synapses. Specifically, we find that KIF5 is required for an efficient
internalization of AMPARs after NMDA receptor activation. We show that the
KIF5/AMPAR complex is assembled in an activity-dependent manner and associates
with microsomal membranes upon LTD induction. This interaction is facilitated by
the vesicular adaptor protrudin, which is also required for LTD expression. We
propose that protrudin links KIF5-dependent transport to endosomal sorting,
preventing AMPAR recycling to synapses after LTD induction. Therefore, this work
identifies an activity-dependent molecular motor and the vesicular adaptor
protein that executes AMPAR synaptic removal during LTD.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.celrep.2021.109499
PMID: 34348158 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.