New paradigms of CFTR chloride channel regulation

The cystic fibrosis transmembrane conductance regulator (CFTR) chloride cha nnel controls salt and water transport across epithelial tissues. Alteratio ns in the activity of this ion channel lead to two major human diseases: cy stic fibrosis (low CFTR activity) and secretory diarrhea (excessive CFTR ac tivity). The goal of this article is to review recent developments in our u nderstanding of two aspects of CFTR biology: (i) interactions between CFTR domains (intramolecular interactions) that control the gating of this epith elial chloride channel and (ii) interactions between CFTR and other protein s (intermolecular interactions) that couple the activity of this ion channe l to additional cellular processes in epithelial cells (e.g. membrane traff ic). Clarifying the nature of these interactions may lead to the developmen t of novel strategies for treating diseases that involve the CFTR chloride channel.