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. (2005) Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors. Journal of Neuroscience, 25 (10). pp. 2682-6. ISSN 0270-6474

URL: http://www.ncbi.nlm.nih.gov/pubmed/15758178
DOI: 10.1523/JNEUROSCI.4834-04.2005

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.

Item Type: Paper
Additional Information:
Uncontrolled Keywords: Animals Calcium Channels biosynthesis physiology Cell Line Dose-Response Relationship Drug Glutamic Acid metabolism pharmacology Humans Protein Binding drug effects physiology Receptors AMPA agonists metabolism Xenopus laevis
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > AMPA receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: CSHL Librarian
Date Deposited: 06 Jan 2012 14:48
Last Modified: 08 Apr 2013 15:13
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22680

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