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Cell Rep. 2019 Jul 2;28(1):11-20.e9. doi: 10.1016/j.celrep.2019.06.005.

Myosin VI Drives Clathrin-Mediated AMPA Receptor Endocytosis to Facilitate Cerebellar Long-Term Depression.

Author information

1
Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: wolfgang.wagner@zmnh.uni-hamburg.de.
2
Carl Ludwig Institute for Physiology, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
3
Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
4
Electron Microscopy Unit, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
5
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), 20139 Milan, Italy; Dipartimento di Oncologia ed Emato-oncologia, Università degli Studi di Milano, 20122 Milan, Italy.
6
Department of Molecular Neurogenetics, Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Electronic address: matthias.kneussel@zmnh.uni-hamburg.de.

Abstract

Myosin VI is an actin-based cytoskeletal motor implicated in various steps of membrane trafficking. Here, we investigated whether this myosin is crucial for synaptic function and plasticity in neurons. We find that myosin VI localizes at cerebellar parallel fiber to Purkinje cell synapses and that the myosin is indispensable for long-term depression of AMPA-receptor-mediated synaptic signal transmission at this synapse. Moreover, direct visualization of GluA2-containing AMPA receptors in Purkinje cells reveals that the myosin drives removal of AMPA receptors from the surface of dendritic spines in an activity-dependent manner. Co-immunoprecipitation and super-resolution microscopy indicate that specifically the interaction of myosin VI with the clathrin adaptor component α-adaptin is important during long-term depression. Together, these data suggest that myosin VI directly promotes clathrin-mediated endocytosis of AMPA receptors in Purkinje cells to mediate cerebellar long-term depression. Our results provide insights into myosin VI function and the molecular mechanisms underlying synaptic plasticity.

KEYWORDS:

AMPA receptor; Myo6; Purkinje cell; actin cytoskeleton; cerebellum; clathrin-mediated endocytosis; dendritic spines; long-term depression; motor protein; myosin; synaptic plasticity

PMID:
31269433
DOI:
10.1016/j.celrep.2019.06.005
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