Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins.

ABSTRACT: Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However, the potential for interactions of these subunits within an AMPA receptor complex is unknown. Here, we find that TARPs ?-4, ?-7, and ?-8, but not ?-2, ?-3, or ?-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With ?-8, resensitization occurs with all GluA subunit combinations; however, ?-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates ?-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, ?-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in ?-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic ?-8-containing AMPA receptors. Thus, ?-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.

SUBMITTER: Kato AS 

PROVIDER: S-EPMC3034222 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature