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

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.

• Publication year

  2003

• Venue

  Journal of Cell Biology

• Publication date

  2003-05-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200212116PMID 12771129PMCID 2199354
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Phosphorylation of the Postsynaptic Density-95 (PSD-95)/Discs Large/Zona Occludens-1 Binding Site of Stargazin Regulates Binding to PSD-95 and Synaptic Targeting of AMPA Receptors

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