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  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. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 25(10), 2682-2686. doi:10.1523/JNEUROSCI.4834-04.2005.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-C5EB-C Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-C5EC-A
Genre: Journal Article
Alternative Title : Stargazin reduces desensitization and slows deactivation of the AMPA-type glutamate receptors

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JNeurosci_25_2005_2682.pdf (Any fulltext), 174KB
 
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 Creators:
Priel, A., Author
Kolleker, Aleksandre1, Author              
Ayalon, G., Author
Gillor, M., Author
Osten, Pavel1, Author              
Stern-Bach, Yael, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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Free keywords: AMPA receptors; stargazin; trafficking; desensitization; patch clamp; heterologous expression
 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.

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Language(s): eng - English
 Dates: 2004-11-262005-01-282005-03-09
 Publication Status: Published in print
 Pages: 5
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
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Title: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 25 (10) Sequence Number: - Start / End Page: 2682 - 2686 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1