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 P2X2e, in mouse pituitary. The P2X2e has a shorter cytoplasmic carboxy-terminal tail than those of full-length P2X2a or splice variant P2X2b subunits. Although ATP induced rapid responses in all homomeric P2X2 channels, the current induced by P2X2e declined significantly faster than those by P2X2a or P2X2b. 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.