Highlights in purinergic signalling

It has become increasingly clear that receptors and ion channels in the plasma membrane do not exist and function in isolation, but instead form complexes with other proteins and this can modify their expression and activity. In this study, the authors determined which proteins complex with the P2X2 receptor and characterised the influence of one, visinin-like protein 1 (VILIP1) on P2X2 receptor expression and activity. They found that P2X2 receptors are part of a complex with nine other proteins and that through a constitutive interaction VILIP1 selectively increased P2X2 receptor expression at the plasma membrane threefold, increased the amplitude of ATP-induced currents by a similar amount and prolonged the life-time of the P2X2 receptor in the plasma membrane. Activation of the P2X2 receptors by ATP increased the association between the two proteins via a conformational change in the P2X2 COOH tail and this effect was dependent on Ca2+ influx through the P2X2 pore. This Ca2+ binds to and most likely causes a conformational change in VILIP1 as well. Thus, the neuronal Ca2+ sensor VILIP1 acts as a regulator of P2X2 receptors