Figure 2.

Diagram of the PIP_n-dependent metabotropic regulation of P2X receptor channels. Membrane-bound PIP_n directly bind a dual polybasic cluster motif found in the C-terminal region of certain P2X receptor subtypes, modulating the current carried through the channel. G protein-coupled receptor (GPCR) or receptor tyrosine kinase (RTK) activation induces PLC-mediated hydrolysis of PI(4,5)P₂, transiently reducing the levels of PI(4,5)P₂ and affecting P2X function. The amino acid sequence of the proximal C-terminal regions of P2X receptors shows the presence of two clusters of basic residues forming a regulatory PIP_n binding site in most subunits.