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 Neurosci
2005 Mar 09;2510:2682-6. doi: 10.1523/JNEUROSCI.4834-04.2005.
Show Gene links
Show Anatomy links
Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors.
Priel A, Kolleker A, Ayalon G, Gillor M, Osten P, Stern-Bach Y.
???displayArticle.abstract???
The AMPA-type glutamate receptors mediate the majority of the fast excitatory synaptic transmission and critically contribute to synaptic plasticity in the brain, hence the existence of numerous trafficking proteins dedicated to regulation of their synaptic delivery and turnover. Stargazin (also termed gamma2) is a member of a recently identified protein family termed transmembrane AMPA receptor regulatory proteins (TARPs). TARPs physically associate with AMPA receptors and participate in their surface delivery and anchoring at the postsynaptic membrane. Here, we report that next to its trafficking roles, stargazin may also act as a positive allosteric modulator of AMPA receptor ion channel function. Coexpression of stargazin with AMPA receptor subunits, either in Xenopus oocytes or in human embryonic kidney 293 cells, significantly reduced receptor desensitization in response to glutamate. Receptor deactivation rates were also slowed, and the recovery from desensitization was accelerated. Structurally, based on the data showing a tight correlation between desensitization and the stability of the AMPA receptor intradimer interface, we propose that binding of stargazin may stabilize the receptor conformation. Functionally, our data suggest that AMPA receptors complexed with stargazin (and possibly also with other TARPs) at the postsynaptic membrane are significantly more responsive to synaptically released glutamate compared with AMPA receptors lacking stargazin/TARP interaction. The putative existence of such two states of synaptic AMPA receptors, with and without stargazin/TARP binding, may provide a novel mechanism for regulation of excitatory synaptic strength during development and/or in synaptic plasticity in the adult brain.
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 Ayalon,
Functional assembly of AMPA and kainate receptors is mediated by several discrete protein-protein interactions.
2001,
Pubmed
,
Xenbase Burgess,
Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.
1999,
Pubmed Chen,
Stargazin differentially controls the trafficking of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate and kainate receptors.
2003,
Pubmed
,
Xenbase Chen,
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms.
,
Pubmed Cuadra,
AMPA receptor synaptic targeting regulated by stargazin interactions with the Golgi-resident PDZ protein nPIST.
2004,
Pubmed Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed Garcia,
SAP90 binds and clusters kainate receptors causing incomplete desensitization.
1998,
Pubmed Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed Hashimoto,
Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer.
1999,
Pubmed Horning,
Regulation of AMPA receptor gating by ligand binding core dimers.
2004,
Pubmed Jones,
The impact of receptor desensitization on fast synaptic transmission.
1996,
Pubmed Klugbauer,
A family of gamma-like calcium channel subunits.
2000,
Pubmed Lerma,
Spermine regulates N-methyl-D-aspartate receptor desensitization.
1992,
Pubmed Letts,
The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.
1998,
Pubmed O'Brien,
Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp.
1999,
Pubmed Patneau,
Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate.
1993,
Pubmed Priel,
Mechanism of ivermectin facilitation of human P2X4 receptor channels.
2004,
Pubmed Schnell,
Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number.
2002,
Pubmed Shi,
Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons.
2001,
Pubmed Stern-Bach,
A point mutation in the glutamate binding site blocks desensitization of AMPA receptors.
1998,
Pubmed Sun,
Mechanism of glutamate receptor desensitization.
2002,
Pubmed Tomita,
Dynamic interaction of stargazin-like TARPs with cycling AMPA receptors at synapses.
2004,
Pubmed
,
Xenbase Tomita,
Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins.
2003,
Pubmed Zamanillo,
Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.
1999,
Pubmed
