QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 9, 2005, 25(10):2682-2686; doi:10.1523/JNEUROSCI.4834-04.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (81) Citing Articles via Google Scholar Google Scholar Articles by Priel, A. Articles by Stern-Bach, Y. Search for Related Content PubMed PubMed Citation Articles by Priel, A. Articles by Stern-Bach, Y.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Stargazin Reduces Desensitization and Slows Deactivation of the AMPA-Type Glutamate Receptors

Avi Priel,¹ Alexander Kolleker,² Gai Ayalon,¹ Moshe Gillor,¹ Pavel Osten,² and Yael Stern-Bach¹

¹The Institute of Basic Dental Sciences, The Hebrew University-Hadassah Dental School, Jerusalem 91120, Israel, and ²Department of Molecular Neurobiology, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany

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 2) 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.

Key words: AMPA receptors; stargazin; trafficking; desensitization; patch clamp; heterologous expression

---

Received Nov 26, 2004; revised January 7, 2005; accepted January 28, 2005.

This article has been cited by other articles:

				C. Sager, J. Terhag, S. Kott, and M. Hollmann 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 J. Biol. Chem., November 20, 2009; 284(47): 32413 - 32424. [Abstract] [Full Text] [PDF]

				S. Dai, D. D. Hall, and J. W. Hell Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels Physiol Rev, April 1, 2009; 89(2): 411 - 452. [Abstract] [Full Text] [PDF]

				K. Menuz, J. L. O'Brien, S. Karmizadegan, D. S. Bredt, and R. A. Nicoll TARP Redundancy Is Critical for Maintaining AMPA Receptor Function J. Neurosci., August 27, 2008; 28(35): 8740 - 8746. [Abstract] [Full Text] [PDF]

				D. E. Featherstone and S. A. Shippy Regulation of Synaptic Transmission by Ambient Extracellular Glutamate Neuroscientist, April 1, 2008; 14(2): 171 - 181. [Abstract] [PDF]

				M. A. Bedoukian, J. D. Whitesell, E. J. Peterson, C. M. Clay, and K. M. Partin The Stargazin C Terminus Encodes an Intrinsic and Transferable Membrane Sorting Signal J. Biol. Chem., January 18, 2008; 283(3): 1597 - 1600. [Abstract] [Full Text] [PDF]

				S. Tomita, R. K. Byrd, N. Rouach, C. Bellone, A. Venegas, J. L. O'Brien, K. S. Kim, O. Olsen, R. A. Nicoll, and D. S. Bredt AMPA receptors and stargazin-like transmembrane AMPA receptor-regulatory proteins mediate hippocampal kainate neurotoxicity PNAS, November 20, 2007; 104(47): 18784 - 18788. [Abstract] [Full Text] [PDF]

				K. Menuz, R. M. Stroud, R. A. Nicoll, and F. A. Hays TARP Auxiliary Subunits Switch AMPA Receptor Antagonists into Partial Agonists Science, November 2, 2007; 318(5851): 815 - 817. [Abstract] [Full Text] [PDF]

				D. A. DiGregorio, J. S. Rothman, T. A. Nielsen, and R. A. Silver Desensitization Properties of AMPA Receptors at the Cerebellar Mossy Fiber Granule Cell Synapse J. Neurosci., August 1, 2007; 27(31): 8344 - 8357. [Abstract] [Full Text] [PDF]

				C. Korber, M. Werner, S. Kott, Z.-L. Ma, and M. Hollmann The Transmembrane AMPA Receptor Regulatory Protein {gamma}4 Is a More Effective Modulator of AMPA Receptor Function than Stargazin ({gamma}2) J. Neurosci., August 1, 2007; 27(31): 8442 - 8447. [Abstract] [Full Text] [PDF]

				C. Korber, M. Werner, J. Hoffmann, C. Sager, M. Tietze, S. M. Schmid, S. Kott, and M. Hollmann Stargazin Interaction with {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate (AMPA) Receptors Is Critically Dependent on the Amino Acid at the Narrow Constriction of the Ion Channel J. Biol. Chem., June 29, 2007; 282(26): 18758 - 18766. [Abstract] [Full Text] [PDF]

				J. J. Crowley, A. G. Carter, and W. G. Regehr Fast Vesicle Replenishment and Rapid Recovery from Desensitization at a Single Synaptic Release Site J. Neurosci., May 16, 2007; 27(20): 5448 - 5460. [Abstract] [Full Text] [PDF]

				A. S. Kato, W. Zhou, A. D. Milstein, M. D. Knierman, E. R. Siuda, J. E. Dotzlaf, H. Yu, J. E. Hale, E. S. Nisenbaum, R. A. Nicoll, et al. New Transmembrane AMPA Receptor Regulatory Protein Isoform, {gamma}-7, Differentially Regulates AMPA Receptors J. Neurosci., May 2, 2007; 27(18): 4969 - 4977. [Abstract] [Full Text] [PDF]

				S. Kott, M. Werner, C. Korber, and M. Hollmann Electrophysiological Properties of AMPA Receptors Are Differentially Modulated Depending on the Associated Member of the TARP Family J. Neurosci., April 4, 2007; 27(14): 3780 - 3789. [Abstract] [Full Text] [PDF]

				S. K. Coleman, T. Moykkynen, C. Cai, L. von Ossowski, E. Kuismanen, E. R. Korpi, and K. Keinanen Isoform-Specific Early Trafficking of AMPA Receptor Flip and Flop Variants J. Neurosci., October 25, 2006; 26(43): 11220 - 11229. [Abstract] [Full Text] [PDF]

				M. A. Bedoukian, A. M. Weeks, and K. M. Partin Different Domains of the AMPA Receptor Direct Stargazin-mediated Trafficking and Stargazin-mediated Modulation of Kinetics J. Biol. Chem., August 18, 2006; 281(33): 23908 - 23921. [Abstract] [Full Text] [PDF]

				F. Deng, M. G. Price, C. F. Davis, M. Mori, and D. L. Burgess Stargazin and other transmembrane AMPA receptor regulating proteins interact with synaptic scaffolding protein MAGI-2 in brain. J. Neurosci., July 26, 2006; 26(30): 7875 - 7884. [Abstract] [Full Text] [PDF]

				C. S. Walker, P. J. Brockie, D. M. Madsen, M. M. Francis, Y. Zheng, S. Koduri, J. E. Mellem, N. Strutz-Seebohm, and A. V. Maricq Reconstitution of invertebrate glutamate receptor function depends on stargazin-like proteins PNAS, July 11, 2006; 103(28): 10781 - 10786. [Abstract] [Full Text] [PDF]

				S. Tomita, M. Sekiguchi, K. Wada, R. A. Nicoll, and D. S. Bredt Stargazin controls the pharmacology of AMPA receptor potentiators PNAS, June 27, 2006; 103(26): 10064 - 10067. [Abstract] [Full Text] [PDF]

				R. A. Nicoll, S. Tomita, and D. S. Bredt Auxiliary Subunits Assist AMPA-Type Glutamate Receptors. Science, March 3, 2006; 311(5765): 1253 - 1256. [Abstract] [Full Text] [PDF]

				Y. Zheng, P. J. Brockie, J. E. Mellem, D. M. Madsen, C. S. Walker, M. M. Francis, and A. V. Maricq SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 glutamate receptors in Caenorhabditis elegans PNAS, January 24, 2006; 103(4): 1100 - 1105. [Abstract] [Full Text] [PDF]

				S. M. Thompson, J. P. Y. Kao, R. H. Kramer, K. E. Poskanzer, R. A. Silver, D. Digregorio, and S. S.-H. Wang Flashy Science: Controlling Neural Function with Light J. Neurosci., November 9, 2005; 25(45): 10358 - 10365. [Full Text] [PDF]

				D. Turetsky, E. Garringer, and D. K. Patneau Stargazin Modulates Native AMPA Receptor Functional Properties by Two Distinct Mechanisms J. Neurosci., August 10, 2005; 25(32): 7438 - 7448. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help