Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins.
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.
Tomita
Susumu
S
Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Chen
Lu
L
Kawasaki
Yoshimi
Y
Petralia
Ronald S
RS
Wenthold
Robert J
RJ
Nicoll
Roger A
RA
Bredt
David S
DS
D000818:Animals; D019921:Biotinylation; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
C113940:Cacng2 protein, mouse; C491911:Cacng2 protein, rat; D015220:Calcium Channels; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018091:Receptors, AMPA