Regions of the amino terminus of the P2X1 receptor required for modification by phorbol ester and mGluR1α receptors
Version of Record online: 1 NOV 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 108, Issue 2, pages 331–340, January 2009
How to Cite
Wen, H. and Evans, R. J. (2009), Regions of the amino terminus of the P2X1 receptor required for modification by phorbol ester and mGluR1α receptors. Journal of Neurochemistry, 108: 331–340. doi: 10.1111/j.1471-4159.2008.05761.x
- Issue online: 10 DEC 2008
- Version of Record online: 1 NOV 2008
- Received June 17, 2008; revised manuscript received October 9, 2008; accepted October 10, 2008.
- P2X receptors;
- protein kinase C;
The potentiation of P2X1 receptor currents by phorbol ester (PMA) treatment and stimulation of mGluR1α receptors was sensitive to inhibition of novel forms of protein kinase C. Potentiation was also reduced by co-expression of an amino terminal P2X1 receptor minigene. Cysteine point mutants of residues Tyr16-Gly30 were expressed in Xenopus oocytes. Peak current amplitudes to ATP for Y16C, T18C and R20C mutants were reduced, however this did not result from a decrease in surface expression of the channels. The majority of the mutants showed changes in the time-course of desensitization of ATP evoked currents indicating the important role of this region in regulation of channel properties. PMA and mGluR1α potentiation was abolished for the mutants Y16C, T18C, R20C, K27C and G30C. Minigenes incorporating either Y16C, K27C, V29C or G30C still inhibited PMA responses. However D17C, T18C or R20C mutant minigenes were no longer effective suggesting that these residues are important for interaction with regulatory factors. These results demonstrate that the conserved YXTXK/R sequence and a region with a conserved glycine residue close to the first transmembrane segment contribute to PMA and GPCR regulation of P2X1 receptors.