Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2009 Nov 20;28447:32413-24. doi: 10.1074/jbc.M109.039891.
Show Gene links
Show Anatomy links
C-terminal domains of transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor regulatory proteins not only facilitate trafficking but are major modulators of AMPA receptor function.
Sager C
,
Terhag J
,
Kott S
,
Hollmann M
.
???displayArticle.abstract???
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptors are essential players in fast synaptic transmission in the vertebrate central nervous system. Their synaptic delivery and localization as well as their electrophysiological properties are regulated by transmembrane AMPA receptor regulatory proteins (TARPs). However, the exact mechanisms of how the four originally designated TARPs (gamma2, gamma3, gamma4, and gamma8) modulate AMPA receptor function remain largely unknown. Previous studies suggested the C-terminal domain (CTD) of gamma2 to mediate increased trafficking and reduced desensitization of AMPA receptors. As it remained unclear whether these findings extend to other TARPs, we set out to investigate and compare the role of the CTDs of the four original TARPs in AMPA receptor modulation. To address this issue, we replaced the TARP CTDs with the CTD of the homologous subunit gamma1, a voltage-dependent calcium channel subunit expressed in skeletal muscle that lacks TARP properties. We analyzed the impact of the resulting chimeras on GluR1 functional properties in Xenopus oocytes and HEK293 cells. Interestingly, the CTDs of all TARPs not only modulate the extent and kinetics of desensitization but also modulate agonist potencies of AMPA receptors. Furthermore, the CTDs are required for TARP-induced modulation of AMPA receptor gating, including conversion of antagonists to partial agonists and constitutive channel openings. Strikingly, we found a special role of the cytoplasmic tail of gamma4, suggesting that the underlying mechanisms of modulation of AMPA receptor function are different among the TARPs. We propose that the intracellularly located CTD is the origin of TARP-specific functional modulation and not merely a facilitator of trafficking.
Armstrong,
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
2000, Pubmed
Armstrong,
Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
2000,
Pubmed
Bats,
The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking.
2007,
Pubmed
Bedoukian,
The stargazin C terminus encodes an intrinsic and transferable membrane sorting signal.
2008,
Pubmed
Brorson,
Selective expression of heteromeric AMPA receptors driven by flip-flop differences.
2004,
Pubmed
Chen,
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms.
,
Pubmed
Cho,
Two families of TARP isoforms that have distinct effects on the kinetic properties of AMPA receptors and synaptic currents.
2007,
Pubmed
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Chu,
Calcium channel gamma subunits provide insights into the evolution of this gene family.
2001,
Pubmed
Cokić,
Stargazin modulates AMPA receptor antagonism.
2008,
Pubmed
,
Xenbase
Hollmann,
Cloned glutamate receptors.
1994,
Pubmed
Honoré,
Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists.
1988,
Pubmed
Jin,
Structural basis for partial agonist action at ionotropic glutamate receptors.
2003,
Pubmed
,
Xenbase
Kato,
New transmembrane AMPA receptor regulatory protein isoform, gamma-7, differentially regulates AMPA receptors.
2007,
Pubmed
Kato,
AMPA receptor subunit-specific regulation by a distinct family of type II TARPs.
2008,
Pubmed
Kohda,
Mutation of a glutamate receptor motif reveals its role in gating and delta2 receptor channel properties.
2000,
Pubmed
Kott,
Electrophysiological properties of AMPA receptors are differentially modulated depending on the associated member of the TARP family.
2007,
Pubmed
,
Xenbase
Kott,
Comparative analysis of the pharmacology of GluR1 in complex with transmembrane AMPA receptor regulatory proteins gamma2, gamma3, gamma4, and gamma8.
2009,
Pubmed
,
Xenbase
Körber,
The transmembrane AMPA receptor regulatory protein gamma 4 is a more effective modulator of AMPA receptor function than stargazin (gamma 2).
2007,
Pubmed
Lee,
Versatile PCR-mediated insertion or deletion mutagenesis.
2004,
Pubmed
Mansour,
Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement.
2001,
Pubmed
Menuz,
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists.
2007,
Pubmed
Milstein,
TARP subtypes differentially and dose-dependently control synaptic AMPA receptor gating.
2007,
Pubmed
Nakagawa,
Structure and different conformational states of native AMPA receptor complexes.
2005,
Pubmed
Nicoll,
Auxiliary subunits assist AMPA-type glutamate receptors.
2006,
Pubmed
Priel,
Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors.
2005,
Pubmed
,
Xenbase
Robert,
AMPA receptor binding cleft mutations that alter affinity, efficacy, and recovery from desensitization.
2005,
Pubmed
Robert,
Subunit interactions and AMPA receptor desensitization.
2001,
Pubmed
Rosenmund,
The tetrameric structure of a glutamate receptor channel.
1998,
Pubmed
Sager,
Functional modulation of AMPA receptors by transmembrane AMPA receptor regulatory proteins.
2009,
Pubmed
Schmid,
A domain linking the AMPA receptor agonist binding site to the ion pore controls gating and causes lurcher properties when mutated.
2007,
Pubmed
,
Xenbase
Schnell,
Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number.
2002,
Pubmed
Soto,
Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors.
2007,
Pubmed
Strutz-Seebohm,
Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3.
2006,
Pubmed
,
Xenbase
Sun,
Mechanism of glutamate receptor desensitization.
2002,
Pubmed
Taverna,
The Lurcher mutation of an alpha-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist.
2000,
Pubmed
Tomita,
Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins.
2003,
Pubmed
Tomita,
Stargazin modulates AMPA receptor gating and trafficking by distinct domains.
2005,
Pubmed
,
Xenbase
Tomita,
Stargazin interacts functionally with the AMPA receptor glutamate-binding module.
2007,
Pubmed
Turetsky,
Stargazin modulates native AMPA receptor functional properties by two distinct mechanisms.
2005,
Pubmed
Vandenberghe,
Stargazin is an AMPA receptor auxiliary subunit.
2005,
Pubmed
Villmann,
Kainate binding proteins possess functional ion channel domains.
1997,
Pubmed
,
Xenbase
Villmann,
Investigation by ion channel domain transplantation of rat glutamate receptor subunits, orphan receptors and a putative NMDA receptor subunit.
1999,
Pubmed
,
Xenbase
Wenthold,
Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons.
1996,
Pubmed
Yamazaki,
A novel action of stargazin as an enhancer of AMPA receptor activity.
2004,
Pubmed
,
Xenbase
Yelshansky,
Block of AMPA receptor desensitization by a point mutation outside the ligand-binding domain.
2004,
Pubmed
,
Xenbase
Ziff,
TARPs and the AMPA receptor trafficking paradox.
2007,
Pubmed
