Functional role of spliced cytoplasmic tails in P2X2-receptor-mediated cellular signaling

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. Posttranscriptional 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 P2X(2) 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 P2X(2) channels, the current induced by P2X2, declined significantly faster than those by P2X(2a) or P2X(2b). In this article, we summarize functional alterations of P2X(2) receptors after splicing reactions. Combinations of different P2X(2) subunit carboxy-termini to form homomeric and heteromeric channels could be a molecular mechanism for promoting functional diversities of ATP-induced cellular signals.