Abstract
In 2014, a slew of structures of glutamate receptors were published, based on crystallography and electron microscopy. Here we review these insights, integrate them with existing knowledge about receptor function and try to understand how the structures relate to the key property of the AMPA receptor – its speed.
References
Ahmed, A.H., Wang, S., Chuang, H.H., and Oswald, R.E. (2011). Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of closed lobe conformations. J. Biol. Chem. 286, 35257–35266.10.1074/jbc.M111.269001Search in Google Scholar
Alle, H., Roth, A., and Geiger, J.R. (2009). Energy-efficient action potentials in hippocampal mossy fibers. Science 325, 1405–1408.10.1126/science.1174331Search in Google Scholar
Armstrong, N. and Gouaux, E. (2000). Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron 28, 165–181.10.1016/S0896-6273(00)00094-5Search in Google Scholar
Armstrong, N., Jasti, J., Beich-Frandsen, M., and Gouaux, E. (2006). Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell 127, 85–97.10.1016/j.cell.2006.08.037Search in Google Scholar
Bartos, M., Vida, I., Frotscher, M., Geiger, J.R., and Jonas, P. (2001). Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network. J. Neurosci. 21, 2687–2698.10.1523/JNEUROSCI.21-08-02687.2001Search in Google Scholar
Benveniste, M. and Mayer, M.L. (1995). Trapping of glutamate and glycine during open channel block of rat hippocampal neuron NMDA receptors by 9-aminoacridine. J. Physiol. 483, 367–384.10.1113/jphysiol.1995.sp020591Search in Google Scholar
Bergles, D.E., Diamond, J.S., and Jahr, C.E. (1999). Clearance of glutamate inside the synapse and beyond. Curr. Opin. Neurobiol. 9, 293–298.10.1016/S0959-4388(99)80043-9Search in Google Scholar
Borschel, W.F., Murthy, S.E., Kasperek, E.M., and Popescu, G.K. (2011). NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers. Nat. Commun. 2, 498.10.1038/ncomms1512Search in Google Scholar PubMed PubMed Central
Braitenberg, V. and Schuz, A. (1998). Cortex: Statistics and Geometry of Neuronal Connectivity (Berlin: Springer).10.1007/978-3-662-03733-1Search in Google Scholar
Carbone, A.L. and Plested, A.J. (2012). Coupled control of desensitization and gating by the ligand binding domain of glutamate receptors. Neuron 74, 845–857.10.1016/j.neuron.2012.04.020Search in Google Scholar PubMed
Cha, A. and Bezanilla, F. (1997). Characterizing voltage-dependent conformational changes in the Shaker K+ channel with fluorescence. Neuron 19, 1127–1140.10.1016/S0896-6273(00)80403-1Search in Google Scholar
Chen, G.Q., Cui, C., Mayer, M.L., and Gouaux, E. (1999). Functional characterization of a potassium-selective prokaryotic glutamate receptor. Nature 402, 817–821.10.1038/45568Search in Google Scholar PubMed
Chen, L., Dürr, K.L., and Gouaux, E. (2014). X-ray structures of AMPA receptor-cone snail toxin complexes illuminate activation mechanism. Science 345, 1021–1026.10.1126/science.1258409Search in Google Scholar PubMed PubMed Central
Christie, L.A., Russell, T.A., Xu, J., Wood, L., Shepherd, G.M., and Contractor, A. (2010). AMPA receptor desensitization mutation results in severe developmental phenotypes and early postnatal lethality. Proc. Natl. Acad. Sci. USA 107, 9412–9417.10.1073/pnas.0908206107Search in Google Scholar PubMed PubMed Central
Cobbs, W.H. and Pugh, E.N. (1987). Kinetics and components of the flash photocurrent of isolated retinal rods of the larval salamander, Ambystoma tigrinum. J. Physiol. 394, 529–572.10.1113/jphysiol.1987.sp016884Search in Google Scholar PubMed PubMed Central
Colquhoun, D. (2007). Why the Schild method is better than Schild realised. Trends Pharmacol. Sci. 28, 608–614.10.1016/j.tips.2007.09.011Search in Google Scholar PubMed
Colquhoun, D., Jonas, P., and Sakmann, B. (1992). Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. J. Physiol. 458, 261–287.10.1113/jphysiol.1992.sp019417Search in Google Scholar PubMed PubMed Central
Cull-Candy, S.G. and Usowicz, M.M. (1987). Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature 325, 525–528.10.1038/325525a0Search in Google Scholar PubMed
Diamond, J.S. and Jahr, C.E. (1997). Transporters buffer synaptically released glutamate on a submillisecond time scale. J. Neurosci. 17, 4672–4687.10.1523/JNEUROSCI.17-12-04672.1997Search in Google Scholar
Dürr, K.L., Chen, L., Stein, R.A., De Zorzi, R., Folea, I.M., Walz, T., Mchaourab, H.S., and Gouaux, E. (2014). Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. Cell 158, 778–792.10.1016/j.cell.2014.07.023Search in Google Scholar PubMed PubMed Central
Dutta, A., Shrivastava, I.H., Sukumaran, M., Greger, I.H., and Bahar, I. (2012). Comparative dynamics of NMDA- and AMPA-glutamate receptor N-terminal domains. Structure 20, 1838–1849.10.1016/j.str.2012.08.012Search in Google Scholar
Frauenfelder, H., Sligar, S.G., and Wolynes, P.G. (1991). The energy landscapes and motions of proteins. Science 254, 1598–1603.10.1126/science.1749933Search in Google Scholar
Gielen, M., Le Goff, A., Stroebel, D., Johnson, J.W., Neyton, J., and Paoletti, P. (2008). Structural rearrangements of NR1/NR2A NMDA receptors during allosteric inhibition. Neuron 57, 80–93.10.1016/j.neuron.2007.11.021Search in Google Scholar
Heine, M., Groc, L., Frischknecht, R., Béïque, J.C., Lounis, B., Rumbaugh, G., Huganir, R.L., Cognet, L., and Choquet, D. (2008). Surface mobility of postsynaptic AMPARs tunes synaptic transmission. Science 320, 201–205.10.1126/science.1152089Search in Google Scholar
Horning, M.S. and Mayer, M.L. (2004). Regulation of AMPA receptor gating by ligand binding core dimers. Neuron 41, 379–388.10.1016/S0896-6273(04)00018-2Search in Google Scholar
Jackson, A.C. and Nicoll, R.A. (2011). The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits. Neuron 70, 178–199.10.1016/j.neuron.2011.04.007Search in Google Scholar PubMed PubMed Central
Jahr, C.E. and Stevens, C.F. (1987). Glutamate activates multiple single channel conductances in hippocampal neurons. Nature 325, 522–525.10.1038/325522a0Search in Google Scholar PubMed
Jin, R., Banke, T.G., Mayer, M.L., Traynelis, S.F., and Gouaux, E. (2003). Structural basis for partial agonist action at ionotropic glutamate receptors. Nat. Neurosci. 6, 803–810.10.1038/nn1091Search in Google Scholar PubMed
Jonas, P. and Sakmann, B. (1992). Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. J. Physiol. 455, 143–171.10.1113/jphysiol.1992.sp019294Search in Google Scholar PubMed PubMed Central
Kaae, B.H., Harpsøe, K., Kastrup, J.S., Sanz, A.C., Pickering, D.S., Metzler, B., Clausen, R.P., Gajhede, M., Sauerberg, P., Liljefors, T., et al. (2007). Structural proof of a dimeric positive modulator bridging two identical AMPA receptor-binding sites. Chem. Biol. 14, 1294–1303.10.1016/j.chembiol.2007.10.012Search in Google Scholar PubMed
Karakas, E. and Furukawa, H. (2014). Crystal structure of a heterotetrameric NMDA receptor ion channel. Science 344, 992–997.10.1126/science.1251915Search in Google Scholar PubMed PubMed Central
Karakas, E., Regan, M.C., and Furukawa, H. (2015). Emerging structural insights into the function of ionotropic glutamate receptors. Trends Biochem. Sci. 40, 328–337.10.1016/j.tibs.2015.04.002Search in Google Scholar PubMed PubMed Central
Kazi, R., Dai, J., Sweeney, C., Zhou, H.X., and Wollmuth, L.P. (2014). Mechanical coupling maintains the fidelity of NMDA receptor-mediated currents. Nat. Neurosci. 17, 914–922.10.1038/nn.3724Search in Google Scholar PubMed PubMed Central
Klein, R.M. and Howe, J.R. (2004). Effects of the lurcher mutation on GluR1 desensitization and activation kinetics. J. Neurosci. 24, 4941–4951.10.1523/JNEUROSCI.0660-04.2004Search in Google Scholar PubMed PubMed Central
Klippenstein, V., Ghisi, V., Wietstruk, M., and Plested, A.J. (2014). Photoinactivation of glutamate receptors by genetically encoded unnatural amino acids. J. Neurosci. 34, 980–991.10.1523/JNEUROSCI.3725-13.2014Search in Google Scholar PubMed PubMed Central
Kohda, K., Wang, Y., and Yuzaki, M. (2000). Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties. Nat. Neurosci. 3, 315–322.10.1038/73877Search in Google Scholar PubMed
Koike, M., Tsukada, S., Tsuzuki, K., Kijima, H., and Ozawa, S. (2000). Regulation of kinetic properties of GluR2 AMPA receptor channels by alternative splicing. J. Neurosci. 20, 2166–2174.10.1523/JNEUROSCI.20-06-02166.2000Search in Google Scholar
Kumar, J. and Mayer, M.L. (2013). Functional insights from glutamate receptor ion channel structures. Annu. Rev. Physiol. 75, 313–337.10.1146/annurev-physiol-030212-183711Search in Google Scholar PubMed PubMed Central
Lau, A.Y. and Roux, B. (2007). The free energy landscapes governing conformational changes in a glutamate receptor ligand-binding domain. Structure 15, 1203–1214.10.1016/j.str.2007.07.015Search in Google Scholar PubMed PubMed Central
Lau, A.Y. and Roux, B. (2011). The hidden energetics of ligand binding and activation in a glutamate receptor. Nat. Struct. Mol. Biol. 18, 283–287.10.1038/nsmb.2010Search in Google Scholar PubMed PubMed Central
Lau, A.Y., Salazar, H., Blachowicz, L., Ghisi, V., Plested, A.J., and Roux, B. (2013). A conformational intermediate in glutamate receptor activation. Neuron 79, 492–503.10.1016/j.neuron.2013.06.003Search in Google Scholar PubMed PubMed Central
Lee, C.-H., Lü, W., Michel, J.C., Goehring, A., Du, J., Song, X., and Gouaux, E. (2014). NMDA receptor structures reveal subunit arrangement and pore architecture. Nature 511, 191–197.10.1038/nature13548Search in Google Scholar PubMed PubMed Central
Lomash, S., Chittori, S., Brown, P., and Mayer, M.L. (2013). Anions mediate ligand binding in Adineta vaga glutamate receptor ion channels. Structure 21, 414–425.10.1016/j.str.2013.01.006Search in Google Scholar PubMed PubMed Central
Manglik, A., Kim, T.H., Masureel, M., Altenbach, C., Yang, Z., Hilger, D., Lerch, M.T., Kobilka, T.S., Thian, F.S., Hubbell, W.L., et al. (2015). Structural insights into the dynamic process of β2-adrenergic receptor signaling. Cell 161, 1101–1111.10.1016/j.cell.2015.04.043Search in Google Scholar PubMed PubMed Central
Meyerson, J.R., Kumar, J., Chittori, S., Rao, P., Pierson, J., Bartesaghi, A., Mayer, M.L., and Subramaniam, S. (2014). Structural mechanism of glutamate receptor activation and desensitization. Nature 514, 328–334.10.1038/nature13603Search in Google Scholar PubMed PubMed Central
Miranda, P., Contreras, J.E., Plested, A.J., Sigworth, F.J., Holmgren, M., and Giraldez, T. (2013). State-dependent FRET reports calcium- and voltage-dependent gating-ring motions in BK channels. Proc. Natl. Acad. Sci. USA 110, 5217–5222.10.1073/pnas.1219611110Search in Google Scholar PubMed PubMed Central
Partin, K.M., Patneau, D.K., and Mayer, M.L. (1994). Cyclothiazide differentially modulates desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor splice variants. Mol. Pharmacol. 46, 129–138.Search in Google Scholar
Patneau, D.K., Vyklicky, L., and Mayer, M.L. (1993). Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate. J. Neurosci. 13, 3496–3509.10.1523/JNEUROSCI.13-08-03496.1993Search in Google Scholar
Plested, A.J. and Mayer, M.L. (2009). AMPA receptor ligand binding domain mobility revealed by functional cross linking. J. Neurosci. 29, 11912–11923.10.1523/JNEUROSCI.2971-09.2009Search in Google Scholar PubMed PubMed Central
Poon, K., Ahmed, A.H., Nowak, L.M., and Oswald, R.E. (2011). Mechanisms of modal activation of GluA3 receptors. Mol. Pharmacol. 80, 49–59.10.1124/mol.111.071688Search in Google Scholar PubMed PubMed Central
Robert, A. and Howe, J.R. (2003). How AMPA receptor desensitization depends on receptor occupancy. J. Neurosci. 23, 847–858.10.1523/JNEUROSCI.23-03-00847.2003Search in Google Scholar
Rosenmund, C., Stern-Bach, Y., and Stevens, C.F. (1998). The tetrameric structure of a glutamate receptor channel. Science 280, 1596–1599.10.1126/science.280.5369.1596Search in Google Scholar PubMed
Rossi, D.J., Oshima, T., and Attwell, D. (2000). Glutamate release in severe brain ischaemia is mainly by reversed uptake. Nature 403, 316–321.10.1038/35002090Search in Google Scholar PubMed
Rossmann, M., Sukumaran, M., Penn, A.C., Veprintsev, D.B., Babu, M.M., and Greger, I.H. (2011). Subunit-selective N-terminal domain associations organize the formation of AMPA receptor heteromers. EMBO J. 30, 959–971.10.1038/emboj.2011.16Search in Google Scholar PubMed PubMed Central
Saviane, C. and Silver, R.A. (2006). Fast vesicle reloading and a large pool sustain high bandwidth transmission at a central synapse. Nature 439, 983–987.10.1038/nature04509Search in Google Scholar PubMed
Schild, H.O. (1947). pA, a new scale for the measurement of drug antagonism. Br. J. Pharmacol. Chemother. 2, 189–206.10.1111/j.1476-5381.1947.tb00336.xSearch in Google Scholar PubMed PubMed Central
Smith, T.C., Wang, L.Y., and Howe, J.R. (2000). Heterogeneous conductance levels of native AMPA receptors. J. Neurosci. 20, 2073–2085.10.1523/JNEUROSCI.20-06-02073.2000Search in Google Scholar
Sobolevsky, A.I., Rosconi, M.P., and Gouaux, E. (2009). X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462, 745–756.10.1038/nature08624Search in Google Scholar PubMed PubMed Central
Sridevi, K., Lakshmikanth, G.S., Krishnamoorthy, G., and Udgaonkar, J.B. (2004). Increasing stability reduces conformational heterogeneity in a protein folding intermediate ensemble. J. Mol. Biol. 337, 699–711.10.1016/j.jmb.2003.12.083Search in Google Scholar PubMed
Sun, Y., Olson, R., Horning, M., Armstrong, N., Mayer, M., and Gouaux, E. (2002). Mechanism of glutamate receptor desensitization. Nature 417, 245–253.10.1038/417245aSearch in Google Scholar PubMed
Suzuki, Y., Goetze, T.A., Stroebel, D., Balasuriya, D., Yoshimura, S.H., Henderson, R.M., Paoletti, P., Takeyasu, K., and Edwardson, J.M. (2013). Visualization of structural changes accompanying activation of N-methyl-D-aspartate (NMDA) receptors using fast-scan atomic force microscopy imaging. J. Biol. Chem. 288, 778–784.10.1074/jbc.M112.422311Search in Google Scholar PubMed PubMed Central
Swanson, G.T., Kamboj, S.K., and Cull-Candy, S.G. (1997). Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. J. Neurosci. 17, 58–69.10.1523/JNEUROSCI.17-01-00058.1997Search in Google Scholar
Taschenberger, H. and von Gersdorff, H. (2000). Fine-tuning an auditory synapse for speed and fidelity: developmental changes in presynaptic waveform, EPSC kinetics, and synaptic plasticity. J. Neurosci. 20, 9162–9173.10.1523/JNEUROSCI.20-24-09162.2000Search in Google Scholar
Taverna, F., Xiong, Z.G., Brandes, L., Roder, J.C., Salter, M.W., and MacDonald, J.F. (2000). The Lurcher mutation of an a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist. J. Biol. Chem. 275, 8475–8479.10.1074/jbc.275.12.8475Search in Google Scholar PubMed
The PyMOL Molecular Graphics System. (2010). Version (1).7. Schrödinger, LLC.Search in Google Scholar
Traynelis, S.F., Wollmuth, L.P., McBain, C.J., Menniti, F.S., Vance, K.M., Ogden, K.K., Hansen, K.B., Yuan, H., Myers, S.J., and Dingledine, R. (2010). Glutamate receptor ion channels: structure, regulation, and function. Pharmacol. Rev. 62, 405–496.10.1124/pr.109.002451Search in Google Scholar PubMed PubMed Central
Unwin, N. and Fujiyoshi, Y. (2012). Gating movement of acetylcholine receptor caught by plunge-freezing. J. Mol. Biol. 422, 617–634.10.1016/j.jmb.2012.07.010Search in Google Scholar PubMed PubMed Central
Walker, C.S., Jensen, S., Ellison, M., Matta, J.A., Lee, W.Y., Imperial, J.S., Duclos, N., Brockie, P.J., Madsen, D.M., Isaac, J.T., et al. (2009). A novel Conus snail polypeptide causes excitotoxicity by blocking desensitization of AMPA receptors. Curr. Biol. 19, 900–908.10.1016/j.cub.2009.05.017Search in Google Scholar PubMed PubMed Central
Yang, Y.M., Aitoubah, J., Lauer, A.M., Nuriya, M., Takamiya, K., Jia, Z., May, B.J., Huganir, R.L., and Wang, L.Y. (2011). GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse. J. Physiol. 589, 4209–4227.10.1113/jphysiol.2011.208066Search in Google Scholar PubMed PubMed Central
Yelshanskaya, M.V., Li, M., and Sobolevsky, A.I. (2014). Structure of an agonist-bound ionotropic glutamate receptor. Science 345, 1070–1074.10.1126/science.1256508Search in Google Scholar PubMed PubMed Central
Zhao, H., Berger, A.J., Brown, P.H., Kumar, J., Balbo, A., May, C.A., Casillas, E., Laue, T.M., Patterson, G.H., Mayer, M.L., et al. (2012). Analysis of high-affinity assembly for AMPA receptor amino-terminal domains. J. Gen. Physiol. 139, 371–388.10.1085/jgp.201210770Search in Google Scholar PubMed PubMed Central
Zhu, S., Stroebel, D., Yao, C.A., Taly, A., and Paoletti, P. (2013). Allosteric signaling and dynamics of the clamshell-like NMDA receptor GluN1 N-terminal domain. Nat. Struct. Mol. Biol. 20, 477–485.10.1038/nsmb.2522Search in Google Scholar PubMed
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Perspectives of molecular neuroscience in health and disease
- HIGHLIGHT: CURRENT CONCE PTS OF PROTECTION AND REGE NERATION IN BRAIN DISORDERS
- The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP
- Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration
- How to build the fastest receptor on earth
- Signaling pathways regulating Homer1a expression: implications for antidepressant therapy
- RAS and downstream RAF-MEK and PI3K-AKT signaling in neuronal development, function and dysfunction
- Defective actin dynamics in dendritic spines: cause or consequence of age-induced cognitive decline?
- Review
- Role of chitinase-like proteins in cancer
- Research Articles/Short Communications
- Cell Biology and Signaling
- Ectopic overexpression of Nanog induces tumorigenesis in non-tumorous fibroblasts
- Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma
- Molecular Medicine
- Increased secretory sphingomyelinase activity in the first trimester of pregnancy in women later developing preeclampsia: a nested case-control study
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Perspectives of molecular neuroscience in health and disease
- HIGHLIGHT: CURRENT CONCE PTS OF PROTECTION AND REGE NERATION IN BRAIN DISORDERS
- The cytoskeleton as a drug target for neuroprotection: the case of the autism- mutated ADNP
- Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration
- How to build the fastest receptor on earth
- Signaling pathways regulating Homer1a expression: implications for antidepressant therapy
- RAS and downstream RAF-MEK and PI3K-AKT signaling in neuronal development, function and dysfunction
- Defective actin dynamics in dendritic spines: cause or consequence of age-induced cognitive decline?
- Review
- Role of chitinase-like proteins in cancer
- Research Articles/Short Communications
- Cell Biology and Signaling
- Ectopic overexpression of Nanog induces tumorigenesis in non-tumorous fibroblasts
- Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma
- Molecular Medicine
- Increased secretory sphingomyelinase activity in the first trimester of pregnancy in women later developing preeclampsia: a nested case-control study