NDLI: Contribution of cytoskeleton to the internalization of AMPA receptors.

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Contribution of cytoskeleton to the internalization of AMPA receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhou, Q. Xiao, M. Nicoll, R. A.
Description	Author Affiliation: Zhou Q ( Departments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, CA 94143, USA.);
Abstract	Trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) at synapses has been suggested to play an important role in the expression of synaptic plasticity. Both the regulated and the constitutive trafficking of synaptic AMPARs are thought to involve the insertion and removal of receptors by means of an exocytotic and endocytotic process, respectively. In contrast, N-methyl-d-aspartate (NMDA) receptors (NMDARs), which are colocalized with AMPARs at excitatory synapses, appear to be much less dynamic. Here, we present evidence supporting the idea that synaptic AMPARs turn over through a constitutive endocytotic process and that glutamate application greatly enhances this turnover of AMPARs. The glutamate-induced internalization of AMPARs requires a rise in postsynaptic Ca(2+). The AMPAR internalization is mimicked by latrunculin A, a drug that selectively depolymerizes actin and is blocked by jasplakinolide, a drug which stabilizes actin filaments. The rate of endocytosis is not altered by glutamate application, whereas a clear enhancement is observed with insulin application. We propose a model in which the glutamate-induced dissociation of AMPARs from their anchor on the postsynaptic membrane involves actin depolymerization, which allows the released AMPARs to segregate from the NMDARs and diffuse to a presumably perisynaptic site, where they become available to an endocytotic machinery and are selectively internalized.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	3
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Actins Physiology Cytoskeleton Depsipeptides Endocytosis Glutamic Acid Hippocampus Neurons Receptors, AMPA Chemistry Animals Biological Transport Bicyclo Compounds, Heterocyclic Pharmacology Cells, Cultured Drug Effects Cytology Marine Toxins Peptides, Cyclic Receptors, N-Methyl-D-Aspartate Thiazoles Thiazolidines Transferrin Metabolism Alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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