Mark L. Mayer, Ph.D.
Section on Neurophysiology and Biophysics
Building 35, Room 3B1002
35 Convent Drive
Bethesda, MD 20892
Ionotropic glutamate receptors (iGluRs) are membrane proteins that act as molecular pores and mediate signal transmission at the majority of excitatory synapses in the mammalian nervous system. The seven iGluR gene families in humans encode 18 subunits, which assemble to form three major functional families named after the ligands that were first used to identify iGluR subtypes in the late 1970s: AMPA, kainate, and NMDA. Given the essential role of iGluRs in normal brain function and development, and mounting evidence that dysfunction of iGluR activity mediates several neurological and psychiatric diseases and damage during stroke, we devote substantial effort to analyzing iGluR function at the molecular level. Atomic resolution structures solved by protein crystallization and X-ray diffraction provide a framework for designing electrophysiological and biochemical experiments aimed at defining the mechanisms underlying ligand recognition, the gating of ion channel activity, and the action of allosteric modulators. Information derived from these experiments will permit the development of subtype-selective antagonists and allosteric modulators with novel therapeutic applications and reveal the inner workings of a complicated protein machine that plays a key role in brain function.
Mayer ML. Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation. Curr Opin Neurobiol. 2011;21(2):283-90.
Kumar J, Schuck P, Mayer ML. Structure and assembly mechanism for heteromeric kainate receptors. Neuron. 2011;71(2):319-31.
Das U, Kumar J, Mayer ML, Plested AJ. Domain organization and function in GluK2 subtype kainate receptors. Proc Natl Acad Sci U S A. 2010;107(18):8463-8.
Meyerson JR, Kumar J, Chittori S, Rao P, Pierson J, Bartesaghi A, Mayer ML, Subramaniam S. Structural mechanism of glutamate receptor activation and desensitization. Nature. 2014;514(7522):328-34.
Han TH, Dharkar P, Mayer ML, Serpe M. Functional reconstitution of Drosophila melanogaster NMJ glutamate receptors. Proc Natl Acad Sci U S A. 2015;112(19):6182-7.
Related Scientific Focus Areas
Biomedical Engineering and Biophysics
This page was last updated on January 5th, 2012