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

Article Details


Kato AS, Gill MB, Ho MT, Yu H, Tu Y, Siuda ER, Wang H, Qian YW, Nisenbaum ES, Tomita S, Bredt DS

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

Neuron. 2010 Dec 22;68(6):1082-96. doi: 10.1016/j.neuron.2010.11.026.

PubMed ID
21172611 [ View in PubMed

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 gamma-4, gamma-7, and gamma-8, but not gamma-2, gamma-3, or gamma-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With gamma-8, resensitization occurs with all GluA subunit combinations; however, gamma-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates gamma-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, gamma-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in gamma-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic gamma-8-containing AMPA receptors. Thus, gamma-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.

DrugBank Data that Cites this Article

NameUniProt ID
Glutamate receptor 1P42261Details
Glutamate receptor 4P48058Details
Glutamate receptor 3P42263Details
Voltage-dependent calcium channel gamma-7 subunitP62955Details
Voltage-dependent calcium channel gamma-4 subunitQ9UBN1Details
Voltage-dependent calcium channel gamma-8 subunitQ8WXS5Details