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PHYSIOLOGY: The protein IRBIT helps epithelial cells secrete fluid

A number of organs, including the lung, intestine, and pancreas, have glands that secrete fluid and HCO3. Abnormal secretion of fluid and HCO3 can cause disease, including cystic fibrosis and pancreatitis. Shmuel Muallem and colleagues, at the University of Texas Southwestern Medical Center, Dallas, have provided new insight into the molecular mechanisms controlling the secretion of fluid and HCO3 by epithelial cells in the mouse pancreatic duct, data that they hope will have implications for understanding cystic fibrosis.

The authors determined that the protein IRBIT coordinates fluid and HCO3 secretion by epithelial cells in the mouse pancreatic duct through its ability to activate two proteins (pNBC1 and CFTR) that are components of different cell surface complexes involved in the transport of HCO3 into and out of epithelial cells. Activation of pNBC1 is required for HCO3 entry into epithelial cells at the basolateral surface and activation of CFTR is required for HCO3 secretion from epithelial cells at the luminal surface. Further analysis revealed that IRBIT seems to activate these two proteins by distinct mechanisms and that it regulates CFTR by reducing the amount of time the channel is closed. Thus, IRBIT is a key coordinator of a central function of epithelial cells expressing CFTR, the protein that is defective in individuals with cystic fibrosis.

TITLE: IRBIT coordinates epithelial fluid and HCO3 secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct

AUTHOR CONTACT:
Shmuel Muallem
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Phone: (214) 645-6008; Fax: (214) 645-6049; E
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