Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins.
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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]
- 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 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
- Polypeptides
Name UniProt ID Glutamate receptor 1 P42261 Details Glutamate receptor 4 P48058 Details Glutamate receptor 3 P42263 Details Voltage-dependent calcium channel gamma-7 subunit P62955 Details Voltage-dependent calcium channel gamma-4 subunit Q9UBN1 Details Voltage-dependent calcium channel gamma-8 subunit Q8WXS5 Details