The calcium-activated chloride channels play a role in numerous physiological processes such as: water and electrolyte secretion, sensory transduction, regulation of vascular tone, cardiac excitability and neuronal excitability. In 2008, the genes that code for the proteins Anoctamine 1 or TMEM16A and Anoctamine 2 or TMEM16B were cloned; these proteins form bona fide calcium-activated chloride channels.
Our group has studied the activation of Anoctamine-1 (TMEM16A) by calcium, voltage, chloride and protons. In addition, we have used quantitative proteomics to identify 93 proteins associated with Anoctamine-1. Although we do not know the functional relevance of most of these interactions, we have demonstrated that cytosolic proteins such as Moesin and Calcineurin, and transmembrane proteins such as the CFTR channel interact with Anoctamine-1 and modulate its activity. We are currently studying how the function of TMEM16A channels depends on both the proteins and the lipids that surround them.
Purinergic receptors are cationic channels activated by extracellular ATP, which are expressed in cells of the nervous system, immune system and other tissues. We have studied the P2X4 and P2X7 receptors, both members of the P2X purinergic receptor family. Although there are 7 members in this family, until 2007 it was believed that P2X7 did not interact with other purinergic receptors. We showed that P2X4 and P2X7 indeed interact with each other through a protein-protein interaction. This interaction is relevant for the physiological functions of mouse macrophages. Also, we have documented the importance of P2X7 in the phagocytosis of yeast and bacteria.