Molecular determinants of AMPA receptor subunit assembly

• Published in: Trends in neurosciences (Regular ed.) Vol. 30; no. 8; pp. 407 - 416
• Main Authors: Greger, Ingo H., Ziff, Edward B., Penn, Andrew C.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2007; Elsevier Science; Elsevier Sequoia S.A
• Subjects: Amino acids; Animals; Base Sequence; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Endoplasmic Reticulum - metabolism; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Humans; Membranes; Molecular biology; Molecular Sequence Data; Nervous system; Neurology; Neurons - metabolism; Protein Conformation; Protein Subunits - chemistry; Protein Subunits - metabolism; Receptors, AMPA - biosynthesis; Receptors, AMPA - chemistry; Receptors, AMPA - metabolism; RNA - metabolism; Structure-Activity Relationship; Vertebrates: nervous system and sense organs; Human; Composition; Central nervous system; Ionic channel; Glutamate receptor; Subunit; Depolarization; Postsynaptic transmission; AMPA receptor; Neuron; Synaptic plasticity; Gating; Endoplasmic reticulum
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2007.06.005

AMPA-type (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) glutamate receptors (AMPARs) mediate post-synaptic depolarization and fast excitatory transmission in the central nervous system. AMPARs are tetrameric ion channels that assemble in the endoplasmic reticulum (ER) in a poorly understood process. The subunit composition determines channel conductance properties and gating kinetics, and also regulates vesicular traffic to and from synaptic sites, and is thus critical for synaptic function and plasticity. The distribution of functionally different AMPARs varies within and between neuronal circuits, and even within individual neurons. In addition, synapses employ channels with specific subunit stoichiometries, depending on the type of input and the frequency of stimulation. Taken together, it appears that assembly is not simply a stochastic process. Recently, progress has been made in understanding the molecular mechanisms underlying subunit assembly and receptor biogenesis in the ER. These processes ultimately determine the size and shape of the postsynaptic response, and are the subject of this review.