New paradigms of CFTR chloride channel regulation

The Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel controls salt and water transport across epithelial tissues. Alterations in the activity of this ion channel lead to two major human diseases: cystic fibrosis (low CFTR activity) and secretory diarrhea (excessive CFTR activity). The goal of this article is to review recent developments in our understanding of two aspects of CFTR biology: (i) interactions between CFTR domains (intramolecular interactions) that control the gating of this epithelial chloride channel and (ii) interactions between CFTR and other proteins (intermolecular interactions) that couple the activity of this ion channel to additional cellular processes in epithelial cells (e.g. membrane traffic). Clarifying the nature of these interactions may lead to the development of novel strategies for treating diseases that involve the CFTR chloride channel. Received 12 October 1999; accepted 31 December 1999