RT Journal Article
SR Electronic
T1 HSP90 regulation of P2X7 receptor function requires an intact cytoplasmic C-terminus
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.115.102988
DO 10.1124/mol.115.102988
A1 Keisuke Migita
A1 Taku Ozaki
A1 shuji Shimoyama
A1 Junko Yamada
A1 Yoshikazu Nikaido
A1 Tomonori Furukawa
A1 Yuko Shiba
A1 Terrance M Egan
A1 Shinya Ueno
YR 2016
UL http://molpharm.aspetjournals.org/content/early/2016/06/14/mol.115.102988.abstract
AB P2X7 receptors (P2X7Rs) are ATP-gated ion channels that display the unusual property of current facilitation during long applications of agonists. Here we show that facilitation disappears in chimeric P2X7Rs containing the C-terminus of the P2X2 receptor (P2X2R), and in a truncated P2X7R missing the cysteine-rich domain of the C-terminus. The chimeric and truncated receptors also show an apparent decreased permeability to NMDG+. The effects of genetically modifying the C-terminus on NMDG+ permeability were mimicked by pre-application of the HSP90 antagonist geldanamycin to the wild-type receptor. Further, the geldanamycin decreased the shift in the reversal potential of the ATP gated current measured under bi-ionic NMDG+/Na+ condition without effecting the ability of the long application of agonist to facilitate current amplitude. Taken together, the results suggest that HSP90 may be essential for stabilization and function of P2X7Rs through an action on the cysteine-rich domain of the cytoplasmic C-terminus.