Mark L. Mayer

National Institutes of Health

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Sriram Subramaniam

University of British Columbia

Gary L. Westbrook

Vollum Institute

Joel R. Meyerson

Takeda (United States)

Eric Gouaux

Oregon Health & Science University

Prashant Rao

Beth Israel Deaconess Medical Center

Sagar Chittori

St. Jude Children's Research Hospital

Janesh Kumar

National Institute of Technology Hamirpur

Ladislav Vyklický

Czech Academy of Sciences, Institute of Physiology

Robert G. Alberstein

University of California, San Diego

Mihaela Serpe

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Cooperative Institutions

National Institutes of Health

Center for Cancer Research

National Cancer Institute

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Howard Hughes Medical Institute

Columbia University

Cancer Institute (WIA)

University of California, San Diego

Health and Human Development (2HD) Research Network

Frederick National Laboratory for Cancer Research

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Glutamate receptors at atomic resolution

Nature (2006)

Mark L. Mayer

Neurotransmitter receptor

10.1038/nature04709

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Citations (271)

Two channels reduced to one

Nature (1987)

Mark L. Mayer

10.1038/325480a0

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Citations (21)

Mechanism of glutamate receptor desensitization

Nature (2002)

Yu Sun Rich Olson Michelle S. Horning N. Armstrong Mark L. Mayer

Neurotransmitter receptor

Light-gated ion channel

Tetramer

10.1038/417245a

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Citations (651)

Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions

Proceedings of the National Academy of Sciences (2009)

Charu Chaudhry Andrew J.R. Plested Peter Schuck Mark L. Mayer

The activity of many ligand-gated ion channels and cell surface receptors is modulated by small molecules and ions, but an understanding of the underlying molecular mechanisms is scarce. For kainate, but not AMPA subtype glutamate receptors, the binding of Na(+) and Cl(-) ions to discrete, electrostatically coupled sites in the extracellular ligand binding domain (LBD) dimer assembly regulates the rate of entry into the desensitized state, which occurs when the dimer interface ruptures and the channel closes. Studies on glutamate receptors have defined the LBD dimer assembly as a key functional unit that controls activation and desensitization. Here we use analytical ultracentrifugation to probe the energetic effects of allosteric ions on kainate receptor dimer stability in solution, using a GluR6 mutant that desensitizes slowly. Our results show that sodium and chloride ions modulate kainate receptor dimer affinity as much as 50-fold, and that removal of either Cl(-) or Na(+) disrupts the dimer. The applicability of a similar allosteric mechanism for modulation of delta2 glutamate receptors by Ca(2+) was also tested. Our results indicate that ions can contribute substantial free energy to active state stabilization in both these receptors, and provide quantitative measurements of the energetic consequences of allosteric ion binding to a ligand-gated ion channel.

Kainate receptor

Cooperative binding

10.1073/pnas.0904175106

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Citations (47)

Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes

Proceedings of the National Academy of Sciences (2015)

Robert G. Alberstein Richard Grey Austin Zimmet David K. Simmons Mark L. Mayer

Significance We report the characterization of two novel glutamate receptor subunits from recently sequenced ctenophore genomes. The origin of vertebrate NMDA subtype ionotropic glutamate receptors (iGluRs), which play a major role in synaptic plasticity and which require both glutamate and glycine for activation of ion channel gating, is not well understood. Using X-ray crystallography of the ligand binding domains of iGluRs from the comb jelly Mnemiopsis leidyi and the sea gooseberry Pleurobrachia bachei , candidates for the earliest lineage metazoans, we discovered that a large subset of these iGluR subunits form glycine receptors. Similarities to modern-day NMDA receptors suggest NMDA and ctenophore receptors may provide clues to the role of iGluRs in the evolution of neural systems in metazoa.

Kainate receptor

Ionotropic glutamate receptor

Conserved sequence

10.1073/pnas.1513771112

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Citations (52)

Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones

Nature (1984)

Mark L. Mayer Gary L. Westbrook Peter B. Guthrie

Aspartic acid

10.1038/309261a0

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