scholarly journals Mapping the Interaction Sites between AMPA Receptors and TARPs Reveals a Role for the Receptor N-Terminal Domain in Channel Gating

Cell Reports ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. 728-740 ◽  
Author(s):  
Ondrej Cais ◽  
Beatriz Herguedas ◽  
Karolina Krol ◽  
Stuart G. Cull-Candy ◽  
Mark Farrant ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Channel Gating ◽  
Interaction Sites ◽  
Terminal Domain

scholarly journals Structural Basis of a Kv7.1 Potassium Channel Gating Module: Studies of the Intracellular C-Terminal Domain in Complex with Calmodulin

Structure ◽  
2014 ◽  
Vol 22 (11) ◽  
pp. 1582-1594 ◽  
Author(s):  
Dana Sachyani ◽  
Meidan Dvir ◽  
Roi Strulovich ◽  
Giancarlo Tria ◽  
William Tobelaim ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Channel Gating ◽  
Structural Basis ◽  
Terminal Domain ◽  
Potassium Channel Gating

scholarly journals Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting

2017 ◽  
Vol 114 (27) ◽  
pp. 7136-7141 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Yujiao J. Sun ◽  
Adam J. Granger ◽  
Jonathan M. Levy ◽  
Sabine M. Blankenship ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Masking Effect ◽  
Synaptic Targeting ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Amino Terminal Domain

The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD. Remarkably, long-term potentiation (LTP) can override the masking effect of the GFP tag. GluA1, but not GluA2, lacking the ATD fails to show LTP. These findings uncover a role for the ATD in subunit-specific synaptic trafficking of AMPARs, both constitutively and during plasticity. How LTP, induced postsynaptically, engages these extracellular trafficking motifs and what specific cleft proteins participate in the process remain to be elucidated.

scholarly journals Molecular Determinants of Interactions between the N-Terminal Domain and the Transmembrane Core That Modulate hERG K+ Channel Gating

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e24674 ◽  
Author(s):  
Jorge Fernández-Trillo ◽  
Francisco Barros ◽  
Angeles Machín ◽  
Luis Carretero ◽  
Pedro Domínguez ◽  
...  
Keyword(s):  
Channel Gating ◽  
K Channel ◽  
Terminal Domain ◽  
Molecular Determinants

scholarly journals Identification of the WW domain-interaction sites in the unstructured N-terminal domain of EBV LMP 2A

FEBS Letters ◽  
2006 ◽  
Vol 581 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Min-Duk Seo ◽  
Sung Jean Park ◽  
Hyun-Jung Kim ◽  
Bong Jin Lee
Keyword(s):  
Domain Interaction ◽  
Ww Domain ◽  
Interaction Sites ◽  
Terminal Domain

scholarly journals Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors

2018 ◽  
Vol 123 (1) ◽  
pp. 130-137 ◽  
Author(s):  
Sudeshna Chatterjee ◽  
Carina Ade ◽  
Caitlin E. Nurik ◽  
Nicole C. Carrejo ◽  
Chayan Dutta ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Conformational Rigidity ◽  
Terminal Domain

scholarly journals Critical role for Orai1 C-terminal domain and TM4 in CRAC channel gating

Cell Research ◽  
2015 ◽  
Vol 25 (8) ◽  
pp. 963-980 ◽  
Author(s):  
Raz Palty ◽  
Cherise Stanley ◽  
Ehud Y Isacoff
Keyword(s):  
Critical Role ◽  
Channel Gating ◽  
Terminal Domain ◽  
Crac Channel

Structure-based analysis of VDAC1: N-terminus location, translocation, channel gating and association with anti-apoptotic proteins

2012 ◽  
Vol 444 (3) ◽  
pp. 475-485 ◽  
Author(s):  
Shay Geula ◽  
Danya Ben-Hail ◽  
Varda Shoshan-Barmatz
Keyword(s):  
Dynamic Equilibrium ◽  
Channel Gating ◽  
Anion Channel ◽  
Cysteine Residue ◽  
Terminal Region ◽  
Voltage Gating ◽  
Site Directed Mutagenesis ◽  
Voltage Dependent Anion Channel ◽  
Terminal Domain ◽  
Apoptotic Proteins

Structural studies place the VDAC1 (voltage-dependent anion channel 1) N-terminal region within the channel pore. Biochemical and functional studies, however, reveal that the N-terminal domain is cytoplasmically exposed. In the present study, the location and translocation of the VDAC1 N-terminal domain, and its role in voltage-gating and as a target for anti-apoptotic proteins, were addressed. Site-directed mutagenesis and cysteine residue substitution, together with a thiol-specific cross-linker, served to show that the VDAC1 N-terminal region exists in a dynamic equilibrium, located within the pore or exposed outside the β-barrel. Using a single cysteine-residue-bearing VDAC1, we demonstrate that the N-terminal region lies inside the pore. However, the same region can be exposed outside the pore, where it dimerizes with the N-terminal domain of a second VDAC1 molecule. When the N-terminal region α-helix structure was perturbed, intra-molecular cross-linking was abolished and dimerization was enhanced. This mutant also displays reduced voltage-gating and reduced binding to hexokinase, but not to the anti-apoptotic proteins Bcl-2 and Bcl-xL. Replacing glycine residues in the N-terminal domain GRS (glycine-rich sequence) yielded less intra-molecular cross-linked product but more dimerization, suggesting that GRS provides the flexibility needed for N-terminal translocation from the internal pore to the channel face. N-terminal mobility may thus contribute to channel gating and interaction with anti-apoptotic proteins.

scholarly journals α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Channels Lacking the N-terminal Domain

2002 ◽  
Vol 277 (51) ◽  
pp. 49662-49667 ◽  
Author(s):  
Arja Pasternack ◽  
Sarah K. Coleman ◽  
Annukka Jouppila ◽  
David G. Mottershead ◽  
Maria Lindfors ◽  
...  
Keyword(s):  
Cell Surface ◽  
Ligand Binding ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Terminal Domain ◽  
Gated Channel ◽  
Surface Ligand ◽  
Amino Acid Binding ◽  
G Protein Coupled

Ionotropic glutamate receptor (iGluR) subunits contain a ∼400-residue extracellular N-terminal domain (“X domain”), which is sequence-related to bacterial amino acid-binding proteins and to class C G-protein-coupled receptors. The X domain has been implicated in the assembly, transport to the cell surface, allosteric ligand binding, and desensitization in various members of the iGluR family, but its actual role in these events is poorly characterized. We have studied the properties of homomeric α-amino-3-hydroxy-5-methylisoxazolepropionate (AMPA)-selective GluR-D glutamate receptors carrying N-terminal deletions. Our analysis indicates that, surprisingly, transport to the cell surface, ligand binding properties, agonist-triggered channel activation, rapid desensitization, and allosteric potentiation by cyclothiazide can occur normally in the complete absence of the X domain (residues 22–402). The relatively intact ligand-gated channel function of a homomeric AMPA receptor in the absence of the X domain indirectly suggests more subtle roles for this domain in AMPA receptors,e.g.in the assembly of heteromeric receptors and in synaptic protein interactions.

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