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Published 27 May 2003. doi:10.1083/jcb.200212116
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© The Rockefeller University Press, 0021-9525/2003/5/805 $5.00
The Journal of Cell Biology, Volume 161, Number 4, 805-816

Article

Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins



Susumu Tomita1, Lu Chen2, Yoshimi Kawasaki1, Ronald S. Petralia3, Robert J. Wenthold3, Roger A. Nicoll1,2 and David S. Bredt1

1 Department of Physiology, University of California, San Francisco, San Francisco, CA 94143
2 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143
3 Laboratory of Neurochemistry, The National Institute on Deafness and Other Communication Disorders/National Institutes of Health, Bethesda, MD 20892

Address correspondence to David S. Bredt, University of California, San Francisco, School of Medicine, 513 Parnassus Ave., San Francisco, CA 94143-0444. Tel.: (415) 476-6310. Fax: (415) 476-4929. E-mail: bredt{at}itsa.ucsf.edu

Functional expression of {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in cerebellar granule cells requires stargazin, a member of a large family of four-pass transmembrane proteins. Here, we define a family of transmembrane AMPA receptor regulatory proteins (TARPs), which comprise stargazin, {gamma}-3, {gamma}-4, and {gamma}-8, but not related proteins, that mediate surface expression of AMPA receptors. TARPs exhibit discrete and complementary patterns of expression in both neurons and glia in the developing and mature central nervous system. In brain regions that express multiple isoforms, such as cerebral cortex, TARP–AMPA receptor complexes are strictly segregated, suggesting distinct roles for TARP isoforms. TARPs interact with AMPA receptors at the postsynaptic density, and surface expression of mature AMPA receptors requires a TARP. These studies indicate a general role for TARPs in controlling synaptic AMPA receptors throughout the central nervous system.

Key Words: synapse; glutamate receptor; plasticity; stargazin; trafficking

The online version of this article includes supplemental material.

* Abbreviations used in this paper: AMPA, {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; DAB, 3',3-diaminobenzidine tetrahydrochloride; EndoH, endoglycosidase H; GluR, glutamate receptor; NMDA, N-methyl-D-aspartate; PDZ, postsynaptic density-95, discs large, zonula occludens; PMP, peripheral myelin protein; PSD, postsynaptic density; TARP, transmembrane AMPA receptor regulatory protein.


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