AMPA receptor assembly: atomic determinants and built-in modulators.

Advances in Experimental Medicine and Biology
Madhav SukumaranIngo H Greger

Abstract

Glutamate-gated ion channels (iGluRs) predominantly operate as heterotetramers to mediate excitatory neurotransmission at glutamatergic synapses. The subunit composition of the receptors determines their targeting to synaptic sites and signalling properties and is therefore a fundamental parameter for neuronal computations. iGluRs assemble as obligatory or preferential heteromers; the mechanisms underlying this selective assembly are only starting to emerge. Here we review recent work in the field and provide an in-depth update on atomic determinants in the assembly domains, which have been facilitated by recent advances in iGluR structural biology. We also discuss the role of alternative RNA processing in the ligand-binding domain, which modulates a central subunit interface and has the capacity to modulate receptor formation in response to external cues. Finally, we review the emerging physiological significance of signalling via distinct iGluR heterotetramers and provide examples of how recruitment of functionally diverse receptors modulates excitatory neurotransmission under physiological and pathological conditions.

Citations

Jun 7, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Catherine L SalussoliaLonnie P Wollmuth
Dec 22, 2017·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Catherine A OpereNajam A Sharif
Nov 11, 2017·Frontiers in Molecular Neuroscience·Jocelyn WidagdoVictor Anggono
Apr 16, 2016·Nature Reviews. Neuroscience·Jeremy M Henley, Kevin A Wilkinson
Mar 22, 2014·The Journal of Biological Chemistry·Tommi MöykkynenKari Keinänen
Jan 6, 2015·The Journal of Physiology·Tim Green, Naushaba Nayeem
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Jan 6, 2015·The Journal of Physiology·Quan GanLonnie P Wollmuth
Mar 8, 2020·The Journal of Physiology·Johansen B AminLonnie P Wollmuth
Apr 16, 2015·Journal of Proteome Research·Mark S LowenthalAyse Dosemeci

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