Numerous functions have been ascribed to the cystic fibrosis transmembrane conductance regulator (CFTR) and all of them rely on the proper trafficking of this protein into the apical plasma membrane. This understanding is based on the finding that the most common mutation, delta F508 CFTR, remains in the endoplasmic reticulum and is degraded. In contrast, drug or temperature rescue allows mutant delta F508 CFTR to become fully glycosylated and traffic to the membrane. To study this phenomenon we are utilizing lipid rafts in which we observe migration of mature CFTR, endogenous or corrected, to a lower buoyant density in a sucrose gradient. We will utilize this assay to assess the impact of other treatments on mutant CFTR. In addition, we will create and evaluate antibodies that will facilitate the detection of this corrected delta F508 at the cell surface. We will identify accessory proteins that participate in this process so that we will gain insight into therapies that can be targeted to moving CFTR from within the cell to its functional location.
Publications
Moser, A. James, A. Gangopadhyay, N. A. Bradbury, K. W. Peters, R. A. Frizzell, R. J. Bridges (2007). Electrogenic bicarbonate secretion by Prairie Dog Gallbladder. Mar 15 epub ahead of print. Am. J. Physiol.
Kreindler, James L., Kathryn W. Peters, Raymond A. Frizzell, Robert J. Bridges (2006). Identification and membrane localization of electrogenic sodium bicarbonate cotransporters in Calu- 3 cells. Biochim. Biophys. Acta. 1762: 704-710.
Liang, X., K.W. Peters, M.B. Butterworth, and R.A. Frizzell (2006). 14-3-3 isoforms are induced by aldosterone and participate in its regulation of epithelial sodium channels. J Biol. Chem. 281: 16323-16332.
Myerburg, Mike. M., Michael B. Butterworth, Erin E. McKenna, Kathryn W. Peters, Raymond A. Frizzell, Thomas R. Kleyman, and Joseph M. Pilewski (2006). Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: a mechanism for sodium hyperabsorption in cystic fibrosis. J. Biol. Chem. 281: 27942-27949.
Wang, H., L. M. Traub, K. M. Weixel, M. J. Hawryluk, N. Shah, R. S. Edinger, C. J. Perry, L. Kester, M. B. Butterworth, K. W. Peters, T. R. Kleyman, R. A. Frizzell, J. P. Johnson (2006). Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin. J. Biol. Chem. 281: 4129-14135.
Peters, K. W., J. Qi, J. P. Johnson, S. C. Watkins, and R. A. Frizzell (2001). Role of SNARE proteins in CFTR and ENaC trafficking. Pfluger’s Arch., Eur. J. Physiol., 443: S65-S69, 2001.
Peters, K.W., J. Qi, S.C. Watkins and Frizzell, R.A. Mechanisms Underlying Regulated CFTR Trafficking, In: Medical Clinics of North America, Whitcomb, D.C., Ulrich, C., Cohn, J., Eds., W. B. Saunders, Philadelphia, pp. 633-640, 2000.
Berger, J. T., J. A. Voynow, K. W. Peters, and M. C. Rose (1999). Respiratory Carcinoma Cell Lines: MUC genes and glycoconjugates. Am. J. Respir. Cell Mol. Biol. 20: 500-510.
Peters, K. W., J.-J. Qi, S. C. Watkins, and R. A. Frizzell (1999). Syntaxin 1A inhibits regulated CFTR trafficking in Xenopus oocytes. Am. J. Physiol. 277: C174-C180.
Qi, J., K. W. Peters, C. Liu, J.-M. Wang, R. S. Edinger, J. P. Johnson, S. C. Watkins, and R. A. Frizzell (1999). Regulation of the amiloride-sensitive epithelial Na channel by syntaxin 1A. J. Biol. Chem. 274: 30345-30348.
