Abstract
THE phenotype of cystic fibrosis (CF) includes abnormalities in transepithelial transport of Cl- (refs 1–5), decreased sialylation and increased sulphation and fucosylation of glycoproteins6–9, and lung colonization with Pseudomonas. It is not apparent how these abnormalities are interrelated, nor how they result from loss of function of the CF gene-encoded transmembrane regulator (CFTR) 10. We have previously shown that that the pH of a secretory granule is regulated by the vesicular conductance for Cl- (ref. 11). Here we find defective acidification in CF cells of the trans–Golgi/fraws-Golgi network, of prelysosomes and of endosomes as a result of diminished Cl- conductance. Sialylation of proteins and lipids is reduced and ligand traffic altered. These abnormalities can result from defective acidification because vacuolar pH regulates glycoprotein processing and ligand transport. The CF phenotype is similar to that of alkalinized cells12 and acidification-defective mutatants13.
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References
Quinton, P. M. Nature 301, 421–422 (1983).
Knowles, M. R. et al. Science 221, 1067–1069 (1983).
Schoumacher, R. A. et al. Nature 330, 752–754 (1987).
Li, M. et al. Nature 331, 358–360 (1988).
Hwang, T. C. et al. Science 244, 1351–1353 (1989).
Boat, T. F. et al. Am. Rev. resp. Dis. 110, 428–441 (1974).
Frates, R. C., Kaizu, T. T. & Last, J. A. Pediatr. Res. 17, 30–34 (1983).
Wesley, A. Forstner, J., Qureshi, R., Mantle, M. & Forstner, G. Pediatr. Res. 17, 65–69 (1983).
Scanlin, T. F., Wang, Y.-M. & Glick, M. C. Pediatr. Res. 19, 368–373 (1985).
Riordan, J. R. et al. Science 245, 1066–1073 (1989).
Barasch, J., Gershon, M. D., Nunez, E. A., Tamir, H. & Al-Awqati, Q. J. Cell Biol. 107, 2137–2147 (1988).
Mellman, I., Fuchs, R. & Helenius, A. A. Rev. Biochem. 55, 663–700 (1986).
Roff, C. F., Fuchs, R., Mellman, I. & Robbins, A. R. J. Cell Biol. 103, 2283–2297 (1986).
Anderson, R. G. W. & Pathak, R. Cell 40, 635–643 (1985).
Griffiths, G., HolflacK, B., Simons, K., Mellman, I. & Kornfeld, S. Cell 52, 329–341 (1988).
Wagner, J. A. et al. Nature 349, 793–796 (1991).
Yamashiro, D. J., Tycko, B., Fluss, S. R. & Maxfield, F. R. Cell 37, 789–800 (1984).
Al-Awqati, Q. A. Rev. Cell Biol. 2, 179–199 (1986).
Pohlentz, G., Klein, D., Schwarzmann, G., Schmitz, D. & Sandhoff, K. Proc. natn. Acad. Sci. 85, 7044–7048 (1988).
Busam, K. & Decker, K. Eur. J. Biochem. 160, 23–30 (1986).
Roseman, S. et al. Meth. Enzym. 8, 354–372 (1966).
Taatjes, D. J. & Roth, J. Eur. J. Cell Biol. 42, 344–350 (1986).
Rosner, H., Wiegandt, H. & Rahmann, H. J. Neurochem. 21, 655–665 (1973).
Svennerholm L. & Fredman, P. Biochim. Biophys. Acta 617, 97–109 (1980).
Fishman, P. H. & Brady, R. O. Science 194, 906–915 (1976).
Dickson, R. B., Willingham, M. C. & Pastan, I. J. Cell Biol. 89, 29–34 (1981).
Klausner, R. D. et al. Proc. natn. Acad. Sci. U.S.A. 80, 2263–2266 (1983).
Johnson, R. G. & Scarpa, A. J. biol Chem. 254, 3750–3760 (1979).
Bae, H. & Verkman, A. S. Nature 348, 637–639 (1990).
Cheng, S. H. et al. Cell 63, 827–834 (1990).
Paulson, J. C., Prieels, J.-P., Glasgow, L. R. & Hill, R. L. J. biol. Chem. 253, 5617–5624 (1978).
Green, E. D., Gruenebaum, J., Bielinska, M., Baenziger, J. U. & Boime, I. Proc. natn. Acad. Sci. U.S.A. 81, 5320–5324 (1984).
Kriven, H. C., Ginsburg, V. & Roberts, D. D. Arch. Biochem. Biophys. 260, 493–496 (1988).
Fishman, P. H., Moss, J. & Vaughan, M. J. biol. Chem. 251, 4490–4494 (1976).
White, J., Kielian, M. & Helenius, A. Q. Rev. Biophys. 16, 151–195 (1983).
Griffiths, G. & Simons, K. Science 234, 438–443 (1986).
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Barasch, J., Kiss, B., Prince, A. et al. Defective acidification of intracellular organelles in cystic fibrosis. Nature 352, 70–73 (1991). https://doi.org/10.1038/352070a0
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DOI: https://doi.org/10.1038/352070a0
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