Mind the gap: Unexpected ways that blood cells talk to each other

Connexins are transmembrane proteins that oligomerise in the plasma membrane to form hemichannels which are essentially ion channels (although they may convey molecules up to 1000Da in or out of cells). When adjacent hemichannel-bearing cells interact hemichannels dock to form gap junctions – allowing direct communication between the cytosol of the cells via intercellular signalling. This is fast and limited by the rate of diffusion and the specific properties of the gap junction – which are dictated by the connexins from which they are formed. Gap junctions are normally found in tissues where rapid and coordinated communication is required, such as in cardiac muscle. In this seminar I will hopefully convince you that the roles of connexins reach far beyond tissues as we traditionally consider them, and also control blood cell function. Specifically we will explore the roles of connexin hemichannels and gap junctions in the control of platelet function, and their importance for normal blood clotting and thrombosis. Our recent studies have revealed a role for connexin which previously had no assigned purpose, and through the development of selective inhibitors and transgenic mice we are exploring its mechanisms of action in this context and its potential as an anti-thrombotic target.