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(A) Structure-function studies of the nucleotide receptor P2X7

Reference	JE412542
Principal Investigator / Supervisor	Professor Richard North
Co-Investigators / Co-Supervisors	Professor Annmarie Surprenant
Institution	University of Sheffield
Department	Biomedical Science
Funding type	Research
Value (£)	59,152
Status	Completed
Type	Research Grant
Start date	28/04/2000
End date	28/10/2000
Duration	6 months

Abstract

The P2X7 receptor is a nucleotide-gated ion channel of the plasma membrane. Activation of the receptor by extracellular ATP not only opens an intrinsic ion channel, but also leads to cell blebbing and eventual lysis. A single sub-unit of the P2X7 receptor is 595 amino acids in length, and is about 35 percent identical to sub-units of P2X1-P2X6 receptors. However, those receptors function only as ATP-gated cation channels, and their activation does not result in cell lysis. The aim of the proposed research is to determine which parts of the P2X7 receptor are critical to the onward transduction of the intracellular signal, which initiates cell blebbing and lysis. This will be done by simultaneous recording of membrane currents by electrophysiological methods, and bleb formation by single cell imaging. These measures will be performed on cells transfected to express the rat or human P2X7 receptor. Chimeras will be constructed between P2X7 receptors and other P2X receptors, to differentiate the domains of the molecule required for ion permeation and for membrane blebbing. The regions of the molecules involved will then be further refined by site-directed mutagenesis. Together with other approaches (e.g. yeast two-hybrid, and far Western to find interacting proteins, blockade of intracellular transduction pathways) the experiments will increase our understanding of the biological role of P2X7 receptors in cell homeostasis and signalling.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	Joint Equipment Initiative 1999 (JE4) [1999]
Funding Scheme	X – not Funded via a specific Funding Scheme

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