The dynamic AMPA receptor extracellular region: a platform for synaptic protein interactions.

The Journal of Physiology
J García-NafríaIngo H Greger

Abstract

AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate fast excitatory neurotransmission and synaptic plasticity. Structures of GluA2 homotetramers in distinct functional states, together with simulations, emphasise the loose architecture of the AMPAR extracellular region (ECR). The ECR encompasses ∼80% of the receptor, and consists of the membrane-distal N-terminal domain (NTD) and ligand-binding domain (LBD), which is fused to the ion channel domain. Minimal contacts within and between layers, together with flexible peptide linkers connecting these three domains give rise to an organisation capable of dynamic rearrangements. This building plan is uniquely suited to engage interaction partners in the crowded environment of synapses, permitting the formation of new binding sites and the loss of existing ones. ECR motions are thereby expected to impact signalling as well as synaptic anchorage and may thereby influence AMPAR clustering during synaptic plasticity.

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Citations

Oct 1, 2016·The Journal of Physiology·Katalin Tóth
Mar 12, 2016·Science·Beatriz HerguedasIngo H Greger
Nov 15, 2018·Frontiers in Cellular Neuroscience·Brian G HiesterMatthew J Kennedy
Apr 16, 2020·Frontiers in Synaptic Neuroscience·Alicia M Purkey, Mark L Dell'Acqua
Feb 1, 2020·The Journal of Physiology·Aichurok Kamalova, Terunaga Nakagawa
Feb 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Chao-Hua JiangYun Stone Shi
Jul 17, 2021·Neuropharmacology·Javier Díaz-Alonso, Roger A Nicoll
Jul 17, 2021·Neuropharmacology·Peter M MatthewsIngo H Greger
Oct 19, 2017·Biochemistry·Edward C Twomey, Alexander I Sobolevsky
Aug 22, 2021·Science Advances·Austin M RamseyThomas A Blanpied

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