Functional Role of Spliced Cytoplasmic Tails in P2X₂-Receptor-Mediated Cellular Signaling

Abstract

P2X receptors belong to a unique family of ligand-gated channels in terms of their molecular architecture, in which the channel subunit has two transmembrane alpha-helixes with a large extracellular loop keeping amino- and carboxy-termini in the cytoplasm. Post-transcriptional modifications of P2X receptors could diversify cellular responsiveness induced by extracellular ATP in anterior pituitary cells and other cell types. Recently, we found a spliced variant P2X₂ transcript, termed P2X_2e, in mouse pituitary. The P2X_2e has a shorter cytoplasmic carboxy-terminal tail than those of full-length P2X_2a or splice variant P2X_2b subunits. Although ATP induced rapid responses in all homomeric P2X₂ channels, the current induced by P2X_2e declined significantly faster than those by P2X_2a or P2X_2b. In this article, we summarize functional alterations of P2X₂ receptors after splicing reactions. Combinations of different P2X₂ subunit carboxy-termini to form homomeric and heteromeric channels could be a molecular mechanism for promoting functional diversities of ATP-induced cellular signals.