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Figure 1. Functional effects of auxiliary subunits. (A–C) Representative whole-cell currents recorded at −60 mV membrane potential from HEK cells expressing GluA2 (A), GluA2-STZ (B), or GluA2-GSG1L (C) in response to 1-s applications of the full agonist Glu alone (3 mM) or application of the partial agonist kainate (KA; 0.5 mM) or Glu in the continuous presence of the positive allosteric modulator cyclothiazide (CTZ; 30 µM). (D) Fraction of nondesensitized receptors (ISS/I0) and KA efficacy (IKA/I0) for GluA2 (black), GluA2-STZ (blue), and GluA2-GSG1L (red). (E) Two-pulse protocol monitoring recovery from desensitization for GluA2-GSG1L activated by Glu. (F) Mean recovery from desensitization measured using the protocol illustrated in E for GluA2 (black), GluA2-STZ (blue), and GluA2-GSG1L (red). The curves through the points are fits with the Hodgkin-Huxley equation with the time constant of recovery from desensitization 15.3 ± 1.1 ms for GluA2, 13.9 ± 0.9 ms for GluA2-STZ, and 164 ± 11 ms for GluA2-GSG1L. Error bars represent SEM. Modified from Twomey et al. (2016, 2017b).
Published: 15 October 2019
Figure 1. Functional effects of auxiliary subunits. (A–C) Representative whole-cell currents recorded at −60 mV membrane potential from HEK cells expressing GluA2 (A), GluA2-STZ (B), or GluA2-GSG1L (C) in response to 1-s applications of the full More about this image found in Functional effects of auxiliary subunits. (A–C) Representative whole-cell ...
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Figure 2. Topology of AMPARs. (A) Structure of a homotetrameric AMPAR composed of GluA2 subunits (PDB accession no. 5WEO) in surface representation viewed parallel to the membrane. Synaptic and cytosolic spaces around the membrane (gray bars) are marked. Each GluA2 subunit is colored individually (A, dark blue; B, coral; C, light blue; D, dark orange). Each domain layer (ATD, LBD, and TMD) is labeled and separated by a dashed gray line. Insets mark top-down views of slices into the surface of each domain layer. (B) Topology of a single AMPAR subunit. The dashed line at the C-terminus indicates that the structure of the CTD is not yet determined, either because it is excluded from constructs or because of conformational heterogeneity.
Published: 15 October 2019
Figure 2. Topology of AMPARs. (A) Structure of a homotetrameric AMPAR composed of GluA2 subunits (PDB accession no. 5WEO ) in surface representation viewed parallel to the membrane. Synaptic and cytosolic spaces around the membrane (gray bars) More about this image found in Topology of AMPARs. (A) Structure of a homotetrameric AMPAR composed of Gl...
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Figure 3. Architecture of an AMPAR–TARP complex. (A and B) Surface representation of an AMPAR (GluA2 homotetramer) bound to four STZ molecules viewed parallel to the membrane (PDB accession no. 5WEO). Each GluA2 subunit is colored individually (A, dark blue; B, coral; C, light blue; D, dark orange). Each domain layer (ATD, LBD, and TMD) is labeled and separated by a dashed gray line. STZ subunits are colored teal or pink. (C) Top-down view of the TMD region, with two different sets of STZ or TARP assembly points (X or Y sites) around the AMPAR TMD marked by dashed lines. (D) Semitransparent surface and structure of a STZ subunit shown in ribbon, rainbow colored from N-terminus (blue) to C-terminus (red). (E) STZ structure shown as ribbon as in D, but with structural features labeled and also rotated 90° for a top-down view. (F) Topology of the STZ subunit. Dashed lines represent areas not clearly resolved in structural studies.
Published: 15 October 2019
Figure 3. Architecture of an AMPAR–TARP complex. (A and B) Surface representation of an AMPAR (GluA2 homotetramer) bound to four STZ molecules viewed parallel to the membrane (PDB accession no. 5WEO ). Each GluA2 subunit is colored individually More about this image found in Architecture of an AMPAR–TARP complex. (A and B) Surface representation of...
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Figure 4. Structures of TARPs and GSG1L. (A-C) Structures of STZ or TARPγ2 (PDB accession no. 5WEO), TARPγ8 (PDB accession no. 6QKC), and GSG1L (PDB accession no. 5VHY) shown in ribbon representation and rainbow colored from N-terminus (blue) to C-terminus (red) viewed parallel to the membrane (top row) or perpendicular to the membrane (bottom row). Structural elements are labeled. (D) Superposition of STZ (teal), TARPγ8 (purple), and GSG1L (red) viewed parallel to the membrane (top) or perpendicular to the membrane (bottom).
Published: 15 October 2019
Figure 4. Structures of TARPs and GSG1L. (A-C) Structures of STZ or TARPγ2 (PDB accession no. 5WEO ), TARPγ8 (PDB accession no. 6QKC ), and GSG1L (PDB accession no. 5VHY ) shown in ribbon representation and rainbow colored from N-terminus More about this image found in Structures of TARPs and GSG1L. (A-C) Structures of STZ or TARPγ2 (PDB acce...
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Figure 5. Sequence alignment for claudins and claudin-fold AMPAR auxiliary subunits. The secondary structure of STZ is shown above the sequence alignment as cylinders (α-helices), arrows (β-strands), or lines (loops). Completely conserved residues are highlighted in yellow. Mostly conserved residues are highlighted in blue (or green for homologous residues). Conserved cysteines forming a disulfide bridge between β3 and β4 are connected by a red bracket. The C-terminal residues are excluded.
Published: 15 October 2019
Figure 5. Sequence alignment for claudins and claudin-fold AMPAR auxiliary subunits. The secondary structure of STZ is shown above the sequence alignment as cylinders (α-helices), arrows (β-strands), or lines (loops). Completely conserved More about this image found in Sequence alignment for claudins and claudin-fold AMPAR auxiliary subunits. ...
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Figure 6. Interfaces in an AMPAR–STZ complex. (A) Structure of an AMPAR (GluA2 homotetramer) bound to four STZ molecules in ribbon representation viewed parallel to the membrane (PDB accession no. 5WEO). The ATD has been excluded. Each GluA2 subunit is colored individually (A, dark blue; B, coral; C, light blue; D, dark orange), and STZ subunits are colored teal (X site) or pink (Y site). Boxed are regions illustrated in C–G. (B) Extracellular view on the TMD from right above the Q/R site. Membrane segments of one AMPAR subunit (B subunit M1-M4) and one STZ subunit (Y site, TM1-4) are labeled. (C) Interface between the LBD of the B subunit from the AMPAR and the β4-TM2 loop preceding the ECH of a X-site STZ molecule (A, inset I). (D) Electrostatic surface for the region shown in C, blue being positively charged, red negatively charged, and white neutral (A, inset I). (E) Potential interaction between an X-site TARP β1-β2 loop and A subunit LBD helix H (A, inset II). (F) Interface between a Y-site TARP TM3-β5 loop and S2-TM4 linker in the C subunit (A, inset III). (G) AMPAR–TARP interface in the TMD (A, inset IV).
Published: 15 October 2019
Figure 6. Interfaces in an AMPAR–STZ complex. (A) Structure of an AMPAR (GluA2 homotetramer) bound to four STZ molecules in ribbon representation viewed parallel to the membrane (PDB accession no. 5WEO ). The ATD has been excluded. Each GluA2 More about this image found in Interfaces in an AMPAR–STZ complex. (A) Structure of an AMPAR (GluA2 homot...
Journal Articles
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Published: 16 January 2019
Figure 1. Relationship between VRAC current activation and cell swelling in a N1E115 neuroblastoma cell. Relative cell volume is measured simultaneously with whole-cell current allowing a direct correlation between VRAC activation and cell More about this image found in Relationship between VRAC current activation and cell swelling in a N1E115 ...
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Published: 16 January 2019
Figure 2. Examples of VRAC single-channel currents in a C6 glioma cell. Top panel shows membrane voltage. Middle panel shows voltage-dependent inactivation of whole-cell current induced by stepping membrane voltage from −80 to 120 mV. Bottom More about this image found in Examples of VRAC single-channel currents in a C6 glioma cell. Top panel sh...
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Published: 16 January 2019
Figure 3. Effect of intracellular ionic strength on VRAC activation in CHO cells. (A) Reduction of intracellular ionic strength increases the rate of swelling-induced current activation. At an ionic strength of 0.04, VRAC activates spontaneously More about this image found in Effect of intracellular ionic strength on VRAC activation in CHO cells. (A)...
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Published: 16 January 2019
Figure 4. Effect of intracellular inorganic ion levels on swelling-induced 3H-taurine efflux in C6 glioma cells. Left panel shows that swelling-induced taurine efflux is an inverse function of the combined intracellular levels of Na+, K+, and Cl More about this image found in Effect of intracellular inorganic ion levels on swelling-induced 3...
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Published: 16 January 2019
Figure 5. Regulation of RVD mechanisms by intracellular ionic strength. Large fluctuations in cytoplasmic ionic strength can disrupt protein structure and function and a host of diverse cellular processes. The differential sensitivity of VRAC More about this image found in Regulation of RVD mechanisms by intracellular ionic strength. Large fluctu...
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Published: 16 January 2019
Figure 6. Effect of intracellular ATP on VRAC activation in N1E115 neuroblastoma cells. (A) Rate of current activation is a saturable function of intracellular ATP concentration. Cells were swollen by a 100-mOsm reduction in bath osmolality. More about this image found in Effect of intracellular ATP on VRAC activation in N1E115 neuroblastoma cell...
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Published: 16 January 2019
Figure 7. Two-dimensional structure of the LRRC8A channel. (A) Structural components of the LRRC8A protein. The protein comprises four regions, extracellular, transmembrane, intracellular, and LRR regions. β, β strand; EL, extracellular loop; H, More about this image found in Two-dimensional structure of the LRRC8A channel. (A) Structural components...
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Published: 16 January 2019
Figure 8. PONDR VL-XT analysis of LRRC8A (black) and LRRC8C (red) intracellular loops (ILs). PONDR scores are aligned with specific amino acid residues, which are shown at the top. Dashed box shows amino acid sequences that diverge significantly More about this image found in PONDR VL-XT analysis of LRRC8A (black) and LRRC8C (red) intracellular loops...
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Published: 16 January 2019
Figure 9. Cartoon illustrating possible mechanism of VRAC regulation by ionic strength and cell swelling-induced mechanical force. LRR region is shown in orange. Mechanical force is represented by the green springs. Conformation of the LRR More about this image found in Cartoon illustrating possible mechanism of VRAC regulation by ionic strengt...
Journal Articles
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Figure 1. Functional classes of iGluRs. (A) iGluRs are divided into AMPA, kainate, and NMDA receptors with multiple subunits cloned in each of these functional classes. (B) EPSCs from central synapses can be divided into fast AMPA or slow NMDA receptor–mediated components in the absence of Mg2+ using the AMPA receptor antagonist CNQX or the NMDA receptor antagonist AP5. The figure is adapted from Traynelis et al. (2010). (C) The relationships between NMDA receptor current response and membrane potential (i.e., holding potential) in the presence and absence of 100 µM extracellular Mg2+ reveal the voltage-dependent Mg2+ block, which is relieved as the membrane potential approaches 0 mV (i.e., with depolarization). Data are from Yi et al. (2018).
Published: 23 July 2018
Figure 1. Functional classes of iGluRs. (A) iGluRs are divided into AMPA, kainate, and NMDA receptors with multiple subunits cloned in each of these functional classes. (B) EPSCs from central synapses can be divided into fast AMPA or slow NMDA More about this image found in Functional classes of iGluRs. (A) iGluRs are divided into AMPA, kainate, a...
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Figure 2. Subunit stoichiometry and subunit arrangement of GluN1/2 NMDA receptors. The crystal structure of the intact GluN1/2B NMDA receptor (the intracellular CTD omitted from structure; Protein Data Bank accession no. 4PE5; Karakas and Furukawa, 2014) definitively demonstrated that GluN1 and GluN2 subunits assemble as heterotetramers with an alternating pattern (i.e., 1-2-1-2). The NMDA receptor is therefore comprised of two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (i.e., GluN1/2 receptors) that form a central cation-permeable channel pore.
Published: 23 July 2018
Figure 2. Subunit stoichiometry and subunit arrangement of GluN1/2 NMDA receptors. The crystal structure of the intact GluN1/2B NMDA receptor (the intracellular CTD omitted from structure; Protein Data Bank accession no. 4PE5 ; Karakas and More about this image found in Subunit stoichiometry and subunit arrangement of GluN1/2 NMDA receptors. T...

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