Why Study Pannexins?

It has long been known that extracellular purine nucleotides (such as ATP), and the ‘purinergic signaling’ that occurs when these purine nucleotides bind to their receptors on responding cells, play a crucial role in physiology of the cardiovascular system as well as for maintaining normal metabolism1-6.  By extension, altered purinergic signaling has been linked to cardiovascular disease, obesity, and metabolic syndromes. However, the ‘gateways’ by which healthy cells release nucleotides in a ‘regulated’ manner are still incompletely understood 2,3,7-12. Interestingly, recent studies also suggest that ATP can be released in a regulated fashion from cells undergoing apoptosis, a form of programmed cell suicide that avoids harm to neighboring cells and inflammation in tissues; the nucleotides released help attract phagocytes to the proximity of the dying cells and facilitate rapid corpse clearance.

Recent work from several laboratories, including members of this UVa Pannexin Team suggest that ATP and other nucleotides can be released from cells via the recently identified and fascinating plasma membrane channels, the Pannexin 1 (Panx1) channels. Besides the fundamental question of how this channel mechanistically regulates various physiological processes, our key interest in these channels stems from the linkage between altered expression of Panx1 in human patients with cardiovascular disease, diabetes, obesity, and airway disease13-22. Since channels typically represent excellent pharmaceutical targets, a better understanding of Panx1 channel function could have implications for developing novel therapeutics for these major human health problems. In this context, our preliminary screens have identified new modifiers of pannexin channel function, suggesting that Panx1 is indeed targetable. Our Pannexin Team at the University of Virginia School of Medicine addresses the function of Panx1 and attempt to understand its relevance and potential therapeutic utility for cardiovascular and metabolic diseases.