Functional expression of α-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, γ-3, γ-4, and γ-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.
Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins
The online version of this article includes supplemental material.
Abbreviations used in this paper: AMPA, α-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.
Susumu Tomita, Lu Chen, Yoshimi Kawasaki, Ronald S. Petralia, Robert J. Wenthold, Roger A. Nicoll, David S. Bredt; Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins . J Cell Biol 26 May 2003; 161 (4): 805–816. doi: https://doi.org/10.1083/jcb.200212116
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