Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors

The Journal of General Physiology
Johansen AminLonnie P Wollmuth

Abstract

Ionotropic glutamate receptors (iGluRs), including AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subtypes, are ligand-gated ion channels that mediate signaling at the majority of excitatory synapses in the nervous system. The iGluR pore domain is structurally and evolutionarily related to an inverted two-transmembrane K+channel. Peripheral to the pore domain in eukaryotic iGluRs is an additional transmembrane helix, the M4 segment, which interacts with the pore domain of a neighboring subunit. In AMPARs, the integrity of the alignment of a specific face of M4 with the adjacent pore domain is essential for receptor oligomerization. In contrast to AMPARs, NMDARs are obligate heterotetramers composed of two GluN1 and typically two GluN2 subunits. Here, to address the function of the M4 segments in NMDARs, we carry out a tryptophan scan of M4 in GluN1 and GluN2A subunits. Unlike AMPARs, the M4 segments in NMDAR subunits makes only a limited contribution to their biogenesis. However, the M4 segments in both NMDAR subunits are critical for receptor activation, with mutations at some positions, most notably at the extreme extracellular end, completely halting the gating process. Furthermore, although the AMPAR M4 makes a minimal con...Continue Reading

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Citations

Apr 24, 2018·Journal of Experimental Botany·Michael M WudickJosé A Feijó
Jun 20, 2018·The Journal of Physiology·Alasdair J GibbStephen F Traynelis
Dec 14, 2018·Frontiers in Physiology·Alice BliznyukYoram Grossman
Jun 20, 2019·Proceedings of the National Academy of Sciences of the United States of America·Mette H PoulsenAndrew J R Plested
Feb 1, 2020·The Journal of Physiology·Aichurok Kamalova, Terunaga Nakagawa
Jul 28, 2019·Scientific Reports·Alice BliznyukYevgeny Moskovitz
Mar 8, 2020·The Journal of Physiology·Johansen B AminLonnie P Wollmuth
Oct 21, 2019·Biophysical Journal·Gary J Iacobucci, Gabriela K Popescu
Jun 4, 2021·Neuropharmacology·Lonnie P WollmuthLaurent Groc
Oct 19, 2017·Biochemistry·Edward C Twomey, Alexander I Sobolevsky
Aug 27, 2021·Cellular and Molecular Neurobiology·Qing-Lin WuNai-Hong Chen

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