Dynamin-Dependent Endocytosis of Ionotropic Glutamate Receptors

Little is known about the mechanisms that regulate the number of ionotropic glutamate receptors present at excitatory synapses. Herein, we show that GluR1-containing α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) are removed from the postsynaptic plasma membrane of c...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-11, Vol.96 (24), p.14112-14117
Main Authors: Carroll, Reed C., Beattie, Eric C., Xia, Houhui, Lüscher, Christian, Altschuler, Yoram, Nicoll, Roger A., Malenka, Robert C., von Zastrow, Mark
Format: Article
Language:English
Subjects:
Adaptor Protein Complex 2
Adaptor Protein Complex alpha Subunits
Adaptor Proteins, Vesicular Transport
Agonists
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism
Animals
Antibodies
Biological Sciences
Cell membranes
Cell surface receptors
Cells, Cultured
clathrin-coated pits
dynamin
Dynamins
Endocytosis
Endocytosis - physiology
GTP Phosphohydrolases - genetics
GTP Phosphohydrolases - metabolism
Hippocampus - cytology
Internalization
Ligands
Membrane Proteins - metabolism
Membranes
Neurology
Neurons
Neurons - cytology
Neurons - metabolism
neurotransmission
Physiological regulation
Rats
Receptors
Receptors, AMPA - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses
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Summary:Little is known about the mechanisms that regulate the number of ionotropic glutamate receptors present at excitatory synapses. Herein, we show that GluR1-containing α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) are removed from the postsynaptic plasma membrane of cultured hippocampal neurons by rapid, ligand-induced endocytosis. Although endocytosis of AMPARs can be induced by high concentrations of AMPA without concomitant activation of N-methyl-D-aspartate (NMDA) receptors (NMDARs), NMDAR activation is required for detectable endocytosis induced by synaptically released glutamate. Activated AMPARs colocalize with AP2, a marker of endocytic coated pits, and endocytosis of AMPARs is blocked by biochemical inhibition of clathrin-coated pit function or overexpression of a dominant-negative mutant form of dynamin. These results establish that ionotropic receptors are regulated by dynamin-dependent endocytosis and suggest an important role of endocytic membrane trafficking in the postsynaptic modulation of neurotransmission.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.24.14112