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1.A.10 The Glutamate-gated Ion Channel (GIC) Family of Neurotransmitter Receptors

Members of the GIC family are homo or heterotetrameric complexes in which each of the 4 subunits is of 800-1000 amino acyl residues in length (Mayer, 2006). These subunits may span the membrane three times as putative transmembrane (TM) α-helices with the N-termini (the glutamate-binding domains) localized extracellularly and the C-termini localized cytoplasmically (Gouaux, 2004).  The extracellular amino terminal domain, S1, and the loop domain between TMSs 2 and 3, bind the neurotransmitter (Gouaux, 2004). Between TMSs 1 and 2 is a P-loop which participates in channel formation and ion selectivity. Transmembrane AMPA receptor regulatory proteins and cornichons allosterically regulate AMPA receptor antagonists and potentiators (Schober et al., 2011; Coombs et al., 2012; Kato et al., 2010).  The 3-d structure of a hetrotetrameric NMDA receptor/ion channel, GluN12GluN22, has been solved to 4 Å resolution (Karakas and Furukawa 2014).  It is a symmetrical dimer of heterodimers.

The extracellular domains of iGluRs are loosely packed assemblies with two clearly distinct layers, each of which has both local and global 2-fold axes of symmetry (Mayer, 2011). By contrast, the GluR transmembrane segments have 4-fold symmetry and share a conserved pore loop architecture found in tetrameric voltage-gated ion channels. The striking layered architecture of iGluRs revealed by the 3.6 Å resolution structure of an AMPA receptor homotetramer likely arose from gene fusion events that occurred early in evolution. Although this modular design has greatly facilitated biophysical and structural studies on individual GluR domains, and suggested conserved mechanisms for iGluR gating, recent work is beginning to reveal unanticipated diversity in the structure, allosteric regulation, and assembly of iGluR subtypes (Mayer, 2011).

The Mammalian ionotropic glutamate receptors (18 proteins) regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. They play important roles in numerous neurological diseases. They have multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. Traynelis et al. (2010) discussed glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, and the potential therapeutic use of pharmacological agents acting at glutamate receptors.

The subunits of GIC family channel proteins fall into six subfamilies: α, β, γ, δ, ε and ζ. Two regions in the N-terminal domain of glutamate receptor 3 form the subunit oligomerization interface that controls subtype-specific receptor assembly (Ayalon et al., 2005). The canonical conformational states occupied by most ligand-gated ion channels, and many cell-surface receptors, are the resting, activated, and desensitized states. The AMPA-sensitive GluR2 receptor undergoes conformational rearrangements of the agonist binding cores that occur upon desensitization. Desensitization involves the rupture of an extensive interface between domain 1 of 2-fold related glutamate-binding core subunits, compensating for the ca. 21 degrees of domain closure induced by glutamate binding. The rupture of the domain 1 interface allows the ion channel to close and thereby provides a simple explanation to the long-standing question of how agonist binding is decoupled from ion channel gating upon receptor desensitization (Armstrong et al., 2006). Auxiliary subunits have been described (Yan and Tomita, 2012).

The GIC channels are divided into three types: (1) α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-, (2) kainate- and (3) N-methyl-D-aspartate (NMDA)-selective glutamate receptors. Subunits of the AMPA and kainate classes exhibit 35-40% identity with each other while subunits of the NMDA receptors exhibit 22-24% identity with the former subunits. They possess large N-terminal, extracellular glutamate-binding domains that are homologous to the periplasmic glutamine and glutamate receptors (TC #3.A.1.3.2 and TC #3.A.1.3.4, respectively) of ABC-type uptake permeases (TC #3.A.1) of Gram-negative bacteria. All functionally characterized members of the GIC family are from animals. The different channel (receptor) types exhibit distinct ion selectivities and conductance properties. The NMDA-selective large conductance channels are highly permeable to monovalent cations and Ca2+. The AMPA- and kainate-selective ion channels are permeable primarily to monovalent cations with only low permeability to Ca2+.

A prokaryotic K+-selective glutamate receptor that binds glutamate and forms K+-selective ion channels has been characterized (Chen et al., 1999). It shows sequence similarity to both glutamate receptors of eukaryotes and to K+ channels of the VIC family (TC #1.A.1). It exhibits 397 amino acyl residues, a signal peptide, and three TMSs flanked by two regions of about 140 residues. It showed highest sequence similarity to the rat δ1 GluR followed by a putative GluR from Arabidopsis thaliana. As a result of these observations, it has been proposed that glutamate receptors of eukaryotes arose from a primordial prokaryotic protein (Chen et al., 1999).

High-resolution structures of the ligand binding core of GluR0, a glutamate receptor ion channel from Synechocystis PCC 6803, have been solved by X-ray diffraction (Mayer et al., 2001). The GluR0 structures reveal homology with bacterial periplasmic binding proteins and the rat GluR2 AMPA subtype neurotransmitter receptor. The ligand binding site is formed by a cleft between two globular alpha/beta domains. L-Glutamate binds in an extended conformation, similar to that observed for glutamine binding protein (GlnBP). However, the L-glutamate γ-carboxyl group interacts exclusively with Asn51 in domain 1, different from the interactions of ligand with domain 2 residues observed for GluR2 and GlnBP. To address how neutral amino acids activate GluR0 gating, Mayer et al. (2001) solved the structure of the binding site complex with L-serine. This revealed solvent molecules acting as surrogate ligand atoms, such that the serine OH group makes solvent-mediated hydrogen bonds with Asn51. The structure of a ligand-free, closed-cleft conformation revealed an extensive hydrogen bond network mediated by solvent molecules. Equilibrium centrifugation analysis revealed dimerization of the GluR0 ligand binding core with a dissociation constant of 0.8 microM. In the crystal, a symmetrical dimer involving residues in domain 1 occurs along a crystallographic 2-fold axis and suggests that tetrameric glutamate receptor ion channels are assembled from dimers of dimers. They propose that ligand-induced conformational changes cause the ion channel to open as a result of an increase in domain 2 separation relative to the dimer interface.

Ionotropic glutamate receptor (GluR) ion channels share structural similarity, albeit an inverted membrane topology, with P-loop channels. Like P-loop channels, prokaryotic GluR subunits (e.g. GluR0 of Synechocystis (TC# 1.A.10.2.1)) have two transmembrane channel-forming segments. In contrast, eukaryotic GluRs have an additional transmembrane segment (M4), located C-terminal to the ion channel core. Although topologically similar to GluR0, mammalian AMPA receptor (GluA1) subunits lacking the M4 segment do not display surface expression. In the AMPA receptor structure, a face in M4 forms intersubunit contacts with the transmembrane helices of the ion channel core (M1 and M3) from another subunit within the homotetramer. Thus, a highly specific interaction of the M4 segment with an adjacent subunit is required for surface expression of AMPA receptors (Salussolia et al., 2011). 

AMPA receptors are homo or heterooligomers of four subunits, GluRA-D (also called GluR1-4). The GluRB subunit of the AMPA receptor, responsible for fast excitatory signaling in the brain and ion selectivity, has been purified in milligram quantities as a homotetramer. It exhibits the expected pharmacological properties. Based on molecular mass and electron microscopic studies, the channel appears to be a dimer of dimers (Safferling et al., 2001). The molecular dimensions are about 11 x 14 x 17 nm, and solvent accessible regions that may form the channel can be seen.

Ligand (neurotransmitter) binding opens the transmembrane pore, but after activation, desensitization results, in which the ligand remains bound, but the ion channel is closed. Using the GluR2 AMPA-sensitive glutamate receptor, Sun et al. (2002) showed (1) that the ligand-binding cores form the dimer interfaces, (2) that stabilization of the intradimer interface reduces desensitization, (3) that destabilization of the intradimer interface enhances desensitization, and (4) receptor activation involves conformational changes within each subunit that result in an increase in the separation of portions of the receptor that are linked to the channel. These results indicate how ligand binding is coupled to channel activation (gating), suggest modes of dimer-dimer interaction in the formation of the tetramer, and show that desensitization results from rearrangement of the dimer interface which disengages the agonist-induced conformational change in the ligand-binding core from the ion channel gate (Sun et al., 2002).

NMDA receptors are always heterotetrameric cation channels that transport Ca2+ with subunits NR1, NR2 and NR3 in an (NR1)2 (NR2)2 or (NR1)2 (NR2)(NR3) arrangement (Furukawa et al., 2005). Glycine binds to NR1, and glutamate binds to NR2 and/or NR3, and simultaneous binding of both agonists as well as relief of Mg2+ blockage by membrane depolarization is required for channel opening.

Crystal structures of the ligand binding core of NR2A with glutamate and of the NR1-NR2A heterodimer with glycine and glutamate bound. The details of subunit:subunit interaction and of channel opening were reported (Furukawa et al., 2005). As a result, many features including the mechanism of allosteric modulation of channel activity (Jin et al., 2005) and the mechanism of dual agonist action (Olson and Gouaux, 2005) were revealed. 

 

Glutamate receptor ligand binding domain dimer assembly is modulated allosterically by ions (Chaudhry et al., 2009). The activities of many ligand-gated ion channels and cell surface receptors are modulated by small molecules and ions. 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), regulates dimer assembly. Dimer assembly then 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. Sodium and chloride ions modulate kainate receptor dimer affinity as much as 50-fold, and removal of either Cl- or Na+ disrupts the dimer (Chaudhry et al., 2009).

Ionotropic glutamate receptors (iGluRs) mediate fast excitatory synaptic transmission in the central nervous system. Upon agonist binding, an iGluR opens to allow the flow of cations and subsequently enters into a desensitized state. Dong and Zhou (2011) reported molecular dynamics simulations of an AMPA-subtype iGluR Channel opening and closing were observed in simulations of the activation and desensitization processes, respectively. The motions of the LBD-TMD linkers along the central axis of the receptor and in the lateral plane contributed cooperatively to channel opening and closing. Glutamatergic mechanisms related to epilepsy have been reviewed by Dingledine (2012).

Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. Agonists and competitive antagonists apparently induce opposite motions of the binding pocket (Du et al., 2012). Agonists, usually small, induce closure of the binding pocket, leading to opening of the channel pore, whereas antagonists, usually large, induce opening of the binding pocket, thereby stabilizing the closed pore.

AMPA receptors (AMPAR) are the main ligand-gated ion channels responsible for the fast excitatory synaptic transmission in the mammalian brain. A number of proteins that interact with AMPAR are known to be involved in the trafficking and localization of the receptor and/or the regulation of receptor channel properties. Additionally, the presence of up to 34 proteins may interact as high-confidence constituents of the AMPAR. The inner core of the receptor complex may consist of the GluA tetramer and four auxiliary proteins comprising transmembrane AMPA receptor regulatory proteins and/or cornichons. The other AMPAR interactors, present in lower amount, may form the outer shell of the AMPAR with a range in size and variability (Li et al. 2013).

Ionotropic glutamate receptors comprise two conformationally different A/C and B/D subunit pairs. Closed channels exhibit fourfold radial symmetry in the transmembrane domain (TMD) but transition to twofold dimer-of-dimers symmetry for extracellular ligand binding and N-terminal domains.  It has been suggested that fourfold pore symmetry persists in the open state (Wilding et al. 2014). 

As noted above, N-Methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors, which mediate most excitatory synaptic transmission in mammalian brains. Calcium permeation triggered by activation of NMDA receptors is the pivotal event for initiation of neuronal plasticity. Karakas and Furukawa 2014 determined the crystal structure of the intact heterotetrameric GluN1-GluN2B NMDA receptor ion channel at 4 angstroms. The NMDA receptors are arranged as a dimer of GluN1-GluN2B heterodimers with the twofold symmetry axis running through the entire molecule composed of an amino terminal domain (ATD), a ligand-binding domain (LBD), and a transmembrane domain (TMD). The ATD and LBD are much more highly packed in the NMDA receptors than non-NMDA receptors, which may explain why ATD regulates ion channel activity in NMDA receptors but not in non-NMDA receptors (Karakas and Furukawa 2014).

The generalized transport reaction catalyzed by GIC family channels is:

Me+ (or Me2+) (out) ⇌ Me+ (or Me2+) (in).

 

This family belongs to the: VIC Superfamily.

References associated with 1.A.10 family:

Alexander, S.P.H. and J.A. Peters. (1997). Receptor and ion channel nomenclature supplement. Trends Pharmacol. Sci. 18: 36-40.
Armstrong, N., J. Jasti, M. Beich-Frandsen, and E. Gouaux. (2006). Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor. Cell 127: 85-97. 17018279
Ayalon, G., E. Segev, S. Elgavish, and Y. Stern-Bach. (2005). Two regions in the N-terminal domain of ionotropic glutamate receptor 3 form the subunit oligomerization interfaces that control subtype-specific receptor assembly. J Biol Chem. 280: 15053-15060. 15703162
Bats, C., D. Soto, D. Studniarczyk, M. Farrant, and S.G. Cull-Candy. (2012). Channel properties reveal differential expression of TARPed and TARPless AMPARs in stargazer neurons. Nat Neurosci. [Epub: Ahead of Print] 22581185
Becchetti, A., S. Pillozzi, R. Morini, E. Nesti, and A. Arcangeli. (2010). New insights into the regulation of ion channels by integrins. Int Rev Cell Mol Biol 279: 135-190. 20797679
Bettler B., J. Boulter, I. Hermans-Borgmeyer, A. O'Shea-Greenfield, E.S. Deneris, C. Moll, U. Borgmeyer, M. Hollmann, S. Heinemann. (1990). Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron. 5: 583-595. 1977421
Chaudhry, C., A.J. Plested, P. Schuck, and M.L. Mayer. (2009). Energetics of glutamate receptor ligand binding domain dimer assembly are modulated by allosteric ions. Proc. Natl. Acad. Sci. USA 106: 12329-12334. 19617541
Chen, G.-Q., C. Cui, M.L. Mayer, and E. Gouaux. (1999). Functional characterization of a potassium-selective prokaryotic glutamate receptor. Nature 402: 817-819. 10617203
Coombs, I.D., D. Soto, M. Zonouzi, M. Renzi, C. Shelley, M. Farrant, and S.G. Cull-Candy. (2012). Cornichons modify channel properties of recombinant and glial AMPA receptors. J. Neurosci. 32: 9796-9804. 22815494
Danielson, E., J. Metallo, and S.H. Lee. (2012). Role of TARP interaction in S-SCAM-mediated regulation of AMPA receptors. Channels (Austin) 6: 393-397. 22878254
Das, U., J. Kumar, M.L. Mayer, and A.J. Plested. (2010). Domain organization and function in GluK2 subtype kainate receptors. Proc. Natl. Acad. Sci. USA 107: 8463-8468. 20404149
Dong, H. and H.X. Zhou. (2011). Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor. Nat Commun 2: 354. 21673675
Du, J., H. Dong, and H.X. Zhou. (2012). Size matters in activation/inhibition of ligand-gated ion channels. Trends Pharmacol Sci. [Epub: Ahead of Print] 22789930
Fisher, J.L. and D.D. Mott. (2012). The auxiliary subunits neto1 and neto2 reduce voltage-dependent inhibition of recombinant kainate receptors. J. Neurosci. 32: 12928-12933. 22973017
Furukawa, H., S.K. Singh, R. Mancusso, and E. Gouaux. (2005). Subunit arrangement and function in NMDA receptors. Nature 438: 185-192. 16281028
Gouaux, E. (2004). Structure and function of AMPA receptors. J. Physiol. 554: 249-253. 14645452
Humeau, Y., D. Reisel, A.W. Johnson, T. Borchardt, V. Jensen, C. Gebhardt, V. Bosch, P. Gass, D.M. Bannerman, M.A. Good, Ø. Hvalby, R. Sprengel, and A. Lüthi. (2007). A pathway-specific function for different AMPA receptor subunits in amygdala long-term potentiation and fear conditioning. J. Neurosci. 27: 10947-10956. 17928436
Jackson, A.C. and R.A. Nicoll. (2011). The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits. Neuron. 70: 178-199. 21521608
Jin, R., S. Clark, A.M. Weeks, J.T. Dudman, E. Gouaux, and K.M. Partin. (2005). Mechanism of positive allosteric modulators acting on AMPA receptors. J. Neurosci. 25: 9027-9036. 16192394
Kamboj, R.K., D.D. Schoepp, S. Nutt, L. Shekter, B. Korczak, R.A. True, V. Rampersad, D.M. Zimmerman, and M.A. Wosnick MA. (1994). Molecular cloning, expression, and pharmacological characterization of humEAA1, a human kainate receptor subunit. J. Neurochem. 62:1-9. 8263508
Kang, J., and F.J. Turano. (2003). The putative glutamate receptor 1.1 (AtGLR1.1) functions as a regulator of carbon and nitrogen metabolism in Arabidopsis thaliana. Proc. Natl. Acad. Sci. U.S.A. 100: 6872-6877. 12738881
Karakas, E. and H. Furukawa. (2014). Crystal structure of a heterotetrameric NMDA receptor ion channel. Science 344: 992-997. 24876489
Kato, A.S., M.B. Gill, H. Yu, E.S. Nisenbaum, and D.S. Bredt. (2010). TARPs differentially decorate AMPA receptors to specify neuropharmacology. Trends Neurosci 33: 241-248. 20219255
Kato, A.S., M.B. Gill, M.T. Ho, H. Yu, Y. Tu, E.R. Siuda, H. Wang, Y.W. Qian, E.S. Nisenbaum, S. Tomita, and D.S. Bredt. (2010). Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron. 68: 1082-1096. 21172611
Kennard, J.T., R. Barmanray, S. Sampurno, E. Ozturk, C.A. Reid, L. Paradiso, G.M. D'Abaco, A.H. Kaye, S.J. Foote, T.J. O'Brien, and K.L. Powell. (2011). Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiol Dis 42: 48-54. 21220022
Kim, K.S., D. Yan, and S. Tomita. (2010). Assembly and stoichiometry of the AMPA receptor and transmembrane AMPA receptor regulatory protein complex. J. Neurosci. 30: 1064-1072. 20089915
Li, K.W., N. Chen, and A.B. Smit. (2013). Interaction proteomics of the AMPA receptor: towards identification of receptor sub-complexes. Amino Acids. [Epub: Ahead of Print] 23344883
Limapichat, W., W.Y. Yu, E. Branigan, H.A. Lester, and D.A. Dougherty. (2013). Key Binding Interactions for Memantine in the NMDA Receptor. ACS Chem Neurosci 4: 255-260. 23421676
Lopez, M.N., T.J. Wilding, and J.E. Huettner. (2013). Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles. J Gen Physiol. [Epub: Ahead of Print] 23940260
Mayer, M.L. (2006). Glutamate receptors at atomic resolution. Nature 440: 456-462. 16554805
Mayer, M.L. (2011). Emerging models of glutamate receptor ion channel structure and function. Structure 19: 1370-1380. 22000510
Mayer, M.L., R. Olson, and E. Gouaux. (2001). Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state. J. Mol. Biol. 311: 815-836. 11518533
Midgett, C.R., A. Gill, and D.R. Madden. (2012). Domain architecture of a calcium-permeable AMPA receptor in a ligand-free conformation. Front Mol Neurosci 4: 56. 22232575
Monyer H., R. Sprengel, R. Schoepfer, A. Herb, M. Higuchi, H. Lomeli, N. Burnashev, B. Sakmann, P.H. Seeburg. (1992). Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science. 256: 1217-1221. 1350383
Nakanishi, N., N.A. Shneider, and R. Axel. (1990). A family of glutamate receptor genes: Evidence for the formation of heteromultimeric receptors with distinct channel properties. Neuron 5: 569-581. 1699567
Olson, R. and E. Gouaux. (2005). Crystal structure of the Vibrio cholerae cytolysin (VCC) pro-toxin and its assembly into a heptameric transmembrane pore. J. Mol. Biol. 350: 997-1016. 15978620
Pozo, K., L.A. Cingolani, S. Bassani, F. Laurent, M. Passafaro, and Y. Goda. (2012). β3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons. Proc. Natl. Acad. Sci. USA 109: 1323-1328. 22232691
Safferling, M., W. Tichelaar, G. Kümmerle, A. Jouppila, A. Kuusinen, K. Keinänen, and D.R. Madden. (2001). First images of a glutamate receptor ion channel: oligomeric state and molecular dimensions of GluRB homomers. Biochemistry 40: 13948-13953. 11705385
Sager, C., D. Tapken, and M. Hollmann. (2011). The C-terminal domains of TARPs: unexpectedly versatile domains. Channels (Austin) 4: 155-158. 20224299
Salussolia, C.L., A. Corrales, I. Talukder, R. Kazi, G. Akgul, M. Bowen, and L.P. Wollmuth. (2011). Interaction of the M4 Segment with Other Transmembrane Segments Is Required for Surface Expression of Mammalian α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors. J. Biol. Chem. 286: 40205-40218. 21930708
Schober, D.A., M.B. Gill, H. Yu, D.L. Gernert, M.W. Jeffries, P.L. Ornstein, A.S. Kato, C.C. Felder, and D.S. Bredt. (2011). Transmembrane AMPA receptor regulatory proteins and cornichon-2 allosterically regulate AMPA receptor antagonists and potentiators. J. Biol. Chem. 286: 13134-13142. 21343286
Schüler, T., I. Mesic, C. Madry, I. Bartholomäus, and B. Laube. (2008). Formation of NR1/NR2 and NR1/NR3 heterodimers constitutes the initial step in N-methyl-D-aspartate receptor assembly. J. Biol. Chem. 283(1): 37-46. 17959602
Siegler Retchless B., Gao W. and Johnson JW. (2012). A single GluN2 subunit residue controls NMDA receptor channel properties via intersubunit interaction. Nat Neurosci. 15(3):406-13. 22246434
Slotboom, D.J., I. Sobczak, W.N. Konings, and J.S. Lolkema. (1999). A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop. Proc. Natl. Acad. Sci. USA 96: 14282-14287. 10588697
Sobolevsky, A.I., M.P. Rosconi, and E. Gouaux. (2009). X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature 462: 745-756. 19946266
Stephens, N.R., Z. Qi, and E.P. Spalding. (2008). Glutamate receptor subtypes evidenced by differences in desensitization and dependence on the GLR3.3 and GLR3.4 genes. Plant Physiol. 146: 529-538. 18162597
Straub, C. and S. Tomita. (2011). The regulation of glutamate receptor trafficking and function by TARPs and other transmembrane auxiliary subunits. Curr Opin Neurobiol. [Epub: Ahead of Print] 21993243
Studniarczyk, D., I. Coombs, S.G. Cull-Candy, and M. Farrant. (2013). TARP γ-7 selectively enhances synaptic expression of calcium-permeable AMPARs. Nat Neurosci 16: 1266-1274. 23872597
Sumioka, A. (2013). Auxiliary subunits provide new insights into regulation of AMPA receptor trafficking. J Biochem 153: 331-337. 23426437
Sun, Y., R. Olson, M. Horning, N. Armstrong, M. Mayer, and E. Gouaux. (2002). Mechanism of glutamate receptor desensitization. Nature 417: 245-253. 12015593
Talukder, I. and L.P. Wollmuth. (2011). Local constraints in either the GluN1 or GluN2 subunit equally impair NMDA receptor pore opening. J Gen Physiol 138: 179-194. 21746848
Traynelis, S.F., L.P. Wollmuth, C.J. McBain, F.S. Menniti, K.M. Vance, K.K. Ogden, K.B. Hansen, H. Yuan, S.J. Myers, and R. Dingledine. (2010). Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62: 405-496. 20716669
Uemura, T., H. Mori, and M. Mishina. (2004). Direct interaction of GluRδ2 with Shank scaffold proteins in cerebellar Purkinje cells. Mol. Cell Neurosci. 26: 330-241. 15207857
Unwin, N. (1993). Neurotransmitter action: Opening of ligand-gated ion channels. Cell 72: 31-41. 7679054
Vance, K.M., N. Simorowski, S.F. Traynelis, and H. Furukawa. (2011). Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. Nat Commun 2: 294. 21522138
Wilding, T.J., M.N. Lopez, and J.E. Huettner. (2014). Radial symmetry in a chimeric glutamate receptor pore. Nat Commun 5: 3349. 24561802
Yan, D. and S. Tomita. (2012). Defined criteria for auxiliary subunits of glutamate receptors. J. Physiol. 590: 21-31. 21946847
Yang, Y.C., C.H. Lee, and C.C. Kuo. (2010). Ionic flow enhances low-affinity binding: a revised mechanistic view into Mg2+ block of NMDA receptors. J. Physiol. 588: 633-650. 20026615
Yuan, H., K.B. Hansen, J. Zhang, T.M. Pierson, T.C. Markello, K.V. Fajardo, C.M. Holloman, G. Golas, D.R. Adams, C.F. Boerkoel, W.A. Gahl, and S.F. Traynelis. (2014). Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy. Nat Commun 5: 3251. 24504326
Zhang, Y.V., J. Ni, and C. Montell. (2013). The molecular basis for attractive salt-taste coding in Drosophila. Science 340: 1334-1338. 23766326