Abstract
We used polarized and nonpolarized colonic cell lines (HT-29) to correlate CFTR function and expression with epithelial cell morphogenesis. Unpolarized cells express levels of CFTR mRNA and protein that are equivalent to those observed in polarized cells, and the extent of CFTR glycosylation is also similar. Despite these similarities in CFTR expression, the polarized cells secreted Cl in response tocAMP, but there was nocAMP-stimulated Cl conductance response in the unpolarized cells. In the polarized cells, CFTR is localized in the apical membrane domain, but in unpolarized cells the protein is retained at a perinuclear location. These findings indicate that a peripheral targeting mechanism, distal to the Golgi cisternae, controls the progression of N-linked glycoproteins like CFTR to the apical membrane. This targeting process does not become active until epithelial cells polarize. It may determine whether mutant forms of CFTR are targeted to the apical membrane.
Similar content being viewed by others
References
Anderson, M. P., Rich, D. P., Gregory, R. J., Smith, A. E. and Welsh, M. J. (1991).Science 251, 679–682.
Bear, C. E., Li, C. H., Kartner, N., Bridges, R. J., Jensen, T. J., Ramjeesingh, M., and Riordan, J. R. (1992).Cell 68, 809–818.
Bradbury, N. A., Jilling, T., Berta, G., Sorscher, E. J., Bridges, R. J. and Kirk, K. L. (1992).Science 256, 530–532.
Cheng, S. H., Gregory, R. J., Marshall, J., Paul, S., Souza, D. W., White, G. A., O'Riordan, C. R. and Smith, A. E. (1990).Cell 63, 827–834.
Collins, F. S. (1992).Science 256, 774–779.
Dorner, A. J., and Kaufman, R. J. (1990).Methods Enzymol. 185, 577–596.
Drumm, M. L., Pope, H. A., Cliff, W. H., Rommens, J. M., Marvin, S. A., Tsui, L.-C., Collins, F. S., Frizzell, R. A., and Wilson, J. M. (1990).Cell 62, 1227–1233.
Gregory, R. J., Cheng, S. H., Rich, D. P., Marshall, J., Paul, S., Hehir, K., Ostedgaard, L., Klinger, K. W., Welsh, M. J., and Smith, A. E. (1990).Nature (London)347, 382–386.
Laboisse, C. L. (1990). InCell and Molecular Biology of Colon Cancer (Augenlicht, L. H., ed.), CRC Press, Boca Raton, Florida, pp. 27–43.
Mays, R. W., and Nelson, W. J. (1992).Chest 101, 505–525.
Morris, A. P., Cunningham, S. A., Benos, D. J., and Frizzell, R. A. (1992).J. Biol. Chem. 267, 5575–5583.
Morris, A. P., Cunningham, S. A., Tousson, A., Benos, D. J., and Frizzell, R. A. (1993).J. Cell Biol., submitted.
Rich, D. P., Anderson, M. P., Gregory, R. J., Cheng, S. H., Paul, S., Jefferson, D. M., McCann, J. D., Klinger, K. W., Smith, A. E., and Welsh, M. J. (1990).Nature (London)347, 358–363.
Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavisc, N., and Chou, J. L. (1989).Science 245, 1066–1073.
Takami, N., Oda, K., Fujiwara, T., and Ikehara, Y. (1990).Eur. J. Biochem. 194, 805–810.
Tresize, A. E. O., and Buchwald, M. (1991).Nature (London)353, 434–437.
Venglarik, C. J., Bridges, R. J., and Frizzell, R. A. (1990).Am. J. Physiol.: Cell Physiol. 259, C358-C364.
Welsh, M. J., Smith, P. L., Fromm, M., and Frizzell, R. A. (1982).Science 218, 1219–1221.
Yoshimura, K., Nakamura, H., Trapnell, B. C., Dalemans, W., Pavirani, A., LeCocq, J. P., and Crystal, R. G. (1991).J. Biol. Chem. 266, 9140–9144.
Zweibaum, A., Laburthe, M., Grasset, E., and Louvard, D. (1991). InThe Gastrointestinal System (Field, M., and Frizzell, R. A., eds.), Vol. IV, American Physiological Society, Washington, D.C., pp. 223–255.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Morris, A.P., Cunningham, S.A. & Frizzell, R.A. CFTR targeting in epithelial cells. J Bioenerg Biomembr 25, 21–26 (1993). https://doi.org/10.1007/BF00768064
Issue Date:
DOI: https://doi.org/10.1007/BF00768064