Probing Intersubunit Interfaces in AMPA-subtype Ionotropic Glutamate Receptors.

Abstract:

:AMPA subtype ionotropic glutamate receptors (iGluRs) mediate the majority of fast neurotransmission across excitatory synapses in the central nervous system. Each AMPA receptor is composed of four multi-domain subunits that are organized into layers of two amino-terminal domain (ATD) dimers, two ligand-binding domain (LBD) dimers, transmembrane domains and carboxy-terminal domains. We introduced cysteine substitutions at the intersubunit interfaces of AMPA receptor subunit GluA2 and confirmed substituted cysteine crosslink formation by SDS-PAGE. The functional consequence of intersubunit crosslinks was assessed by recording GluA2-mediated currents in reducing and non-reducing conditions. Strong redox-dependent changes in GluA2-mediated currents were observed for cysteine substitutions at the LBD dimer-dimer interface but not at the ATD dimer-dimer interface. We conclude that during gating, LBD dimers undergo significant relative displacement, while ATD dimers either maintain their relative positioning, or their relative displacement has no appreciable effect on AMPA receptor function.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Yelshanskaya MV,Saotome K,Singh AK,Sobolevsky AI

doi

10.1038/srep19082

subject

Has Abstract

pub_date

2016-01-07 00:00:00

pages

19082

issn

2045-2322

pii

srep19082

journal_volume

6

pub_type

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