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Research Paper
PIP2 Regulates the Ionic Current of P2X Receptors and P2X7 Receptor-Mediated Cell Death
Qi Zhao, Min Yang, Adrian T. Ting and Diomedes E. Logothetis
volume 1 | issue 1
January/February 2007Pages: 46 - 55
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P2X7 receptors are non-selective cation channels gated by extracellular ATP. Prolonged stimulation of the P2X7 receptor leads to an increase in cell permeability, cytokine release and apoptosis/necrosis. Application of PIP2 to inside-out patches strongly activated all homomeric members of the P2X receptor family, including P2X7 channels. Blockade of PIP2 re-synthesis or induction of PIP2 hydrolysis diminished the ATP-gated P2X7 currents. Several positively charged residues in the proximal C-terminus of P2X7 were found to be important for PIP2 interactions, as mutation of these sites reduced the apparent affinity for PIP2 and enhanced current inhibition by PIP2 depletion. In addition, we demonstrated the dependence on the interaction of the receptor with PIP2 of ATP-mediated cell death in HEK cells stably transfected with P2X7, in primary T cells and in macrophages. These results identify PIP2 as a critical regulator of the function of the extracellular ligand-gated P2X receptor/channels and provide a novel way to control ATP-mediated cell death.
Authors
Qi Zhao
Mount Sinai School of Medicine, New York, NY
Min Yang
Adrian T. Ting
Mount Sinai School of Medicine, New York University, New York, NY
Diomedes E. Logothetis
Mount Sinai School of Medicine, New York University, New York, NY
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.