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0031-6997/05/5702-253-277$7.00
Pharmacol Rev 57:253-277, 2005

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Article

The Molecular Pharmacology and Cell Biology of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors

Claire L. Palmer, Lucy Cotton and Jeremy M. Henley

Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, Bristol University, Bristol, United Kingdom

Abstract
I. Introduction
    A. Classes of Glutamate Receptors
    B. AMPA Receptor Topology
        1. The N Terminus.
        2. Hydrophobic Regions.
        3. The Intracellular C Terminus.
    C. Pharmacology
    D. Post-Transcriptional Modification
        1. Splice Variants.
        2. RNA Editing.
    E. Post-Translational Modification
        1. Glycosylation.
        2. Phosphorylation.
            a. GluR1.
            b. GluR2.
            c. GluR3.
            d. GluR4.
    F. Expression Patterns
        1. Regional Distribution in the Brain.
        2. Neuronal and Glial Expression.
        3. Developmental Regulation.
        4. Subcellular Expression Patterns.
    G. Plasma Membrane Distribution of AMPA Receptors
        1. Postsynaptic Membrane.
        2. Extrasynaptic AMPA Receptors.
        3. Presynaptic Terminal.
II. Trafficking of AMPA Receptors
    A. Assembly
    B. Visualizing AMPA Receptor Translocation
    C. Lateral Diffusion of AMPA Receptors in the Membrane
    D. AMPA Receptor Delivery to Synapses
    E. AMPA Receptor Turnover at Synapses
    F. Trafficking, Learning, and Memory
III. Interacting Proteins
    A. PDZ-Containing Proteins
        1. PDZ Architecture.
        2. AMPA Receptor Binding Protein/Glutamate Receptor-Interacting Protein.
        3. LIN-10.
        4. Protein Interacting with C Kinase.
        5. Synapse-Associated Protein-97.
        6. SemaF Cytoplasmic Domain-Associated Protein-3 and PDZ-Regulator of G-Protein Signaling-3.
        7. Syntenin.
        8. Transmembrane AMPA Receptor Regulatory Proteins.
    B. Other Interactors
        1. Neuronal Activity-Regulated Pentraxin.
        2. N-Ethylmaleimide-Sensitive Factor.
        3. 4.1.
IV. Future Directions
Abstract

{alpha}-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are of fundamental importance in the brain. They are responsible for the majority of fast excitatory synaptic transmission, and their overactivation is potently excitotoxic. Recent findings have implicated AMPARs in synapse formation and stabilization, and regulation of functional AMPARs is the principal mechanism underlying synaptic plasticity. Changes in AMPAR activity have been described in the pathology of numerous diseases, such as Alzheimer's disease, stroke, and epilepsy. Unsurprisingly, the developmental and activity-dependent changes in the functional synaptic expression of these receptors are under tight cellular regulation. The molecular and cellular mechanisms that control the postsynaptic insertion, arrangement, and lifetime of surface-expressed AMPARs are the subject of intense and widespread investigation. For example, there has been an explosion of information about proteins that interact with AMPAR subunits, and these interactors are beginning to provide real insight into the molecular and cellular mechanisms underlying the cell biology of AMPARs. As a result, there has been considerable progress in this field, and the aim of this review is to provide an account of the current state of knowledge.

Address correspondence to: Professor Jeremy M. Henley, Assistant Director MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, Bristol, BS8 1TD. E-mail: j.m.henley{at}bristol.ac.uk




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