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N-glycans as apical sorting signals in epithelial cells

Naturevolume 378pages9698 (1995) | Download Citation

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Abstract

IN epithelial Madin–Darby canine kidney (MDCK) cells newly synthesized molecules are sorted in the trans-Golgi network and directly delivered to their apical and basolateral surface destinations1. Sorting is mediated by signals in the cytoplasmic domains of basolateral transmembrane proteins2–4 whereas gly-cosylphosphatidylinositol-linked proteins have apical sorting information in their glycolipid tails5,6. Signals for apical transmembrane proteins are thought to reside in their ectodomains, because truncated forms lacking the cytoplasmic tail and the membrane anchor are secreted apically7,8. Here we demonstrate that carbohydrates act as an apical targeting signal for secretory proteins. Growth hormone, which is non-glycosylated and secreted from both sides of MDCK cell layers9, is secreted from the apical side when gly-cosylated. Thus glycans not only play a general role in protein folding10 but also appear to function in protein sorting in biosynthetic traffic.

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References

  1. 1

    Wandinger-Ness, A., Bennet, M. K., Antony, C. & Simons, K. J. Cell Biol. 111, 987–1000 (1990).

  2. 2

    Hunziker, W., Harter, C., Matter, K. & Mellman, I. Cell 66, 1–20 (1991).

  3. 3

    Mostov, K. E., Harris, J. M. & Breitfeld, P. P. J. Cell Biol. 105, 2031–2036 (1987).

  4. 4

    Matter, K. & Mellman, I. Curr. Opin. Cell Biol. 6, 545–554 (1994).

  5. 5

    Brown, D. A., Crise, B. & Rose, J. K. Science 245, 1499–1501 (1989).

  6. 6

    Lisanti, M. P., Caras, I. W., Davitz, M. A. & Rodriguez-Boulan, E. J. Cell Biol. 109, 2145–2156 (1989).

  7. 7

    Corbeil, D., Boileau, G., Lemay, G. & Crine, P. J. biol. Chem. 267, 2798–2801 (1992).

  8. 8

    Vogel, L. K., Spiess, M., Sjöström, H. & Norén, O. J. biol. Chem. 267, 2794–2797 (1992).

  9. 9

    Gottlieb, T. A. et al. Proc. natn. Acad. Sci. U.S.A. 83, 2100–2104 (1986).

  10. 10

    Helenius, A. Molec. Biol. Cell 5, 253–265 (1994).

  11. 11

    Green, R. F., Meiss, H. K. & Rodriguez-Boulan, E. J. J. Cell Biol. 89, 230–239 (1981).

  12. 12

    Urban, J., Parczyk, K., Leutz, A., Kayne, M. & Kondor-Koch, C. J. Cell Biol. 105, 2735–2743 (1987).

  13. 13

    Guan, J.-L., Machamer, C. E. & Rose, J. K. Cell 42, 489–496 (1985).

  14. 14

    Balcarova-Ständer, J., Pfeiffer, S. E., Fuller, S. D. & Simons, K. EMBO J. 3, 2687–2694 (1984).

  15. 15

    Kondor-Koch, C. B., Bravo, R., Fuller, S. D., Cutler, D. & Garoff, H. Cell 43, 297–306 (1985).

  16. 16

    Cunningham, B. C., Mulkerrin, M. G. & Wells, J. A. Science 253, 545–548 (1991).

  17. 17

    Chanat, E. & Huttner, W. B. J. Cell Biol. 115, 1505–1519 (1991).

  18. 18

    Gonzalez, A., Nicovani, S. & Juica, F. J. biol. Chem. 268, 6662–6667 (1993).

  19. 19

    Fiedler, K. & Simons, K. Cell 81, 1–20 (1995).

  20. 20

    Musto, N. A. Expl Cell Res. 209, 271–276 (1993).

  21. 21

    Kitagawa, Y. et al. Expl Cell Res. 213, 449–457 (1994).

  22. 22

    Vogel, L. K., Suske, G., Beato, M., Norén, O. & Sjöström, H. FEBS Lett. 330, 293–296 (1993).

  23. 23

    Meiss, H. K., Green, R. F. & Rodriguez-Boulan, E., Molec. cell. Biol. 2, 1287–1294 (1982).

  24. 24

    Wagner, M., Morgans, C. & Koch-Brandt, C. Eur. J. Cell Biol. 67, 84–88 (1995).

  25. 25

    Fiedler, K., Parton, R. G., Kellner, R., Etzold, T. & Simons, K. EMBO J. 13, 1729–1740 (1994).

  26. 26

    Caplan, M. J. et al. Nature 329, 632–635 (1987).

  27. 27

    Ragno, P. et al. Expl Cell Res. 203, 236–243 (1992).

  28. 28

    Rodriguez-Boulan, E. & Powell, S. K. A. Rev. Cell Biol. 8, 395–427 (1992).

  29. 29

    Casanova, J. E., Breitfeld, P. P., Ross, S. A. & Mostov, K. E. Science 248, 742–745 (1990).

  30. 30

    Miller, A. D. & Rosman, G. M. Biotechniques 7, 980–990 (1989).

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  1. Kai Simons: To whom correspondence should be addressed.

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  1. Cell Biology Programme, European Molecular Biology Laboratory, Postfach 102229, 69112, Heidelberg, Germany

    • Peter Scheiffele
    • , Johan Peränen
    •  & Kai Simons

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https://doi.org/10.1038/378096a0

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