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The Journal of Neuroscience, August 27, 2008, 28(35):8740-8746; doi:10.1523/JNEUROSCI.1319-08.2008

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Cellular/Molecular
TARP Redundancy Is Critical for Maintaining AMPA Receptor Function

Karen Menuz,¹ Jessica L. O'Brien,¹ Siavash Karmizadegan,² David S. Bredt,² and Roger A. Nicoll^1,2

Departments of ¹Cellular and Molecular Pharmacology and ²Physiology, University of California, San Francisco, San Francisco, California 94143

Correspondence should be addressed to Roger A. Nicoll, Department of Cellular and Molecular Pharmacology, 600 16th Street, N272-D, University of California, San Francisco, San Francisco, CA 94143. Email: nicoll{at}cmp.ucsf.edu

Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary subunits that influence diverse aspects of receptor function. However, the full complement of physiological roles for TARPs in vivo remains poorly understood. Here we find that double knock-out mice lacking TARPs -2 and -3 are profoundly ataxic and fail to thrive. We demonstrate that these TARPs are critical for the synaptic targeting and kinetics of AMPA receptors in cerebellar Golgi cells, but that either alone is sufficient to fully preserve function. By analyzing the few remaining synaptic AMPA receptors in the -2, -3 double knock-out mice, we unexpectedly find that these TARPs specify AMPA receptor subunit composition. This study establishes a new role for TARPs in regulating AMPA receptor assembly and suggests that TARPs are necessary for proper AMPA receptor localization and function in most, if not all, neurons of the CNS.

Key words: glutamate receptor; auxiliary subunit; synaptic transmission; Golgi cell; stargazin; stargazer; interneuron

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Received March 27, 2008; revised July 18, 2008; accepted July 24, 2008.

Correspondence should be addressed to Roger A. Nicoll, Department of Cellular and Molecular Pharmacology, 600 16th Street, N272-D, University of California, San Francisco, San Francisco, CA 94143. Email: nicoll{at}cmp.ucsf.edu

This article has been cited by other articles:

				S. Tomita Regulation of Ionotropic Glutamate Receptors by Their Auxiliary Subunits Physiology, February 1, 2010; 25(1): 41 - 49. [Abstract] [Full Text] [PDF]

				J. Schwenk, N. Harmel, G. Zolles, W. Bildl, A. Kulik, B. Heimrich, O. Chisaka, P. Jonas, U. Schulte, B. Fakler, et al. Functional Proteomics Identify Cornichon Proteins as Auxiliary Subunits of AMPA Receptors Science, March 6, 2009; 323(5919): 1313 - 1319. [Abstract] [Full Text] [PDF]

				K. Menuz and R. A. Nicoll Loss of Inhibitory Neuron AMPA Receptors Contributes to Ataxia and Epilepsy in Stargazer Mice J. Neurosci., October 15, 2008; 28(42): 10599 - 10603. [Abstract] [Full Text] [PDF]

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