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Proc Natl Acad Sci U S A
2006 Jun 27;10326:10064-7. doi: 10.1073/pnas.0603128103.
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Stargazin controls the pharmacology of AMPA receptor potentiators.
Tomita S, Sekiguchi M, Wada K, Nicoll RA, Bredt DS.
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Glutamate is the major excitatory neurotransmitter in brain, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) mediate the majority of postsynaptic depolarization. AMPAR ion channels display rapid gating, and their deactivation and desensitization determine the timing of synaptic transmission. AMPAR potentiators slow channel deactivation and desensitization, and these compounds represent exciting therapies for mental and neurodegenerative diseases. Previous studies showed that the AMPAR potentiators cyclothiazide and 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide display a preference for flip and flop alternatively spliced versions of glutamate receptor subunits, respectively. Here, we find that the AMPAR auxiliary subunit stargazin changes this pharmacology and makes both spliced forms of glutamate receptor subunit 1 sensitive to both classes of potentiator. Stargazin also enhances the effect of AMPAR potentiators on channel deactivation. This work demonstrates that stargazin controls AMPAR potentiator pharmacology, which has important implications for development of AMPAR potentiators as therapeutic agents.
Bredt,
AMPA receptor trafficking at excitatory synapses.
2003, Pubmed
Bredt,
AMPA receptor trafficking at excitatory synapses.
2003,
Pubmed Chen,
Stargazin differentially controls the trafficking of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate and kainate receptors.
2003,
Pubmed
,
Xenbase Fleck,
AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide.
1996,
Pubmed Furukawa,
Subunit arrangement and function in NMDA receptors.
2005,
Pubmed Hollmann,
Cloned glutamate receptors.
1994,
Pubmed Jin,
Mechanism of positive allosteric modulators acting on AMPA receptors.
2005,
Pubmed Jonas,
The Time Course of Signaling at Central Glutamatergic Synapses.
2000,
Pubmed Li,
Enhancement of antidepressant potency by a potentiator of AMPA receptors.
2003,
Pubmed Longone,
Changes in AMPA receptor-spliced variant expression and shift in AMPA receptor spontaneous desensitization pharmacology during cerebellar granule cell maturation in vitro.
1998,
Pubmed Lynch,
Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.
1997,
Pubmed O'Neill,
Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson's disease.
2004,
Pubmed Partin,
AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate.
1996,
Pubmed Partin,
Cyclothiazide differentially modulates desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor splice variants.
1994,
Pubmed
,
Xenbase Porrino,
Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates.
2005,
Pubmed Priel,
Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors.
2005,
Pubmed
,
Xenbase Seeburg,
The TINS/TiPS Lecture. The molecular biology of mammalian glutamate receptor channels.
1993,
Pubmed Sekiguchi,
A desensitization-selective potentiator of AMPA-type glutamate receptors.
2002,
Pubmed
,
Xenbase Sekiguchi,
A novel allosteric potentiator of AMPA receptors: 4--2-(phenylsulfonylamino)ethylthio--2,6-difluoro-phenoxyaceta mide.
1997,
Pubmed
,
Xenbase Sekiguchi,
The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment.
2001,
Pubmed Sommer,
Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS.
1990,
Pubmed Staubli,
Facilitation of glutamate receptors enhances memory.
1994,
Pubmed Sun,
Mechanism of glutamate receptor desensitization.
2002,
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,
Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses.
2004,
Pubmed
,
Xenbase
