Probing Intersubunit Interfaces in AMPA-subtype Ionotropic Glutamate Receptors

• DOI: 10.1038/srep19082
• Publication Date: 2016-01-07T10:06:55Z
• Authors: Maria V. Yelshans...; Kei Saotome; Appu K. Singh; Alexander I. Sobo...
• Keywords: Kainate receptor; Ionotropic glutamate receptor

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