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The mechanism of protein secretion across membranes

Nature volume 283, pages 433–438 (1980)Cite this article

Abstract

Many secreted proteins are synthesised as a large precursor with an additional hydrophobic N-terminal signal sequence that is cleaved by a membrane-bound enzyme. The proteins are secreted as nascent chains. The work leading to the current models of protein secretion is reviewed and the value of bacterial systems in the study of protein transfer across membranes is stressed.

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References

  1. Palade, G. E. J. Biophys. Biochem. Cytol. 1, 59–68 (1955).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Palade, G. E. Science 189, 347–358 (1975).

    ADS  CAS  PubMed  Google Scholar 

  3. Rolleston, F. S. Sub-Cell. Biochem. 3, 91–117 (1974).

    CAS  Google Scholar 

  4. Redman, C. M. & Sabatini, D. D. Prroc. natn. Acad. Sci. U.S.A. 56, 608–615 (1966).

    ADS  CAS  Google Scholar 

  5. Blobel, G. & Sabatini, D. D. in Biomembranes Vol. 2 (ed. Manson, L. A.) 193–195 (Plenum, New York, 1971).

    Google Scholar 

  6. Milstein, C., Brownlee, G. G., Harrison, T. M. & Mathews, M. B. Nature new Biol. 239, 117–120 (1972).

    CAS  PubMed  Google Scholar 

  7. Cowan, N. J., Harrison, T. M., Brownlee, G. G. & Milstein, C. Biochem. Soc. Trans. 1, 1247–1250 (1973).

    Google Scholar 

  8. Swan, D., Aviv, H. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 69, 1967–1971 (1972).

    ADS  CAS  Google Scholar 

  9. Mach, B., Faust, C. & Vassalli, P. Proc. natn. Acad. Sci. U.S.A., 70, 451–455 (1973).

    ADS  CAS  Google Scholar 

  10. Schechter, I. Proc. natn. Acad. Sci. U.S.A. 70, 2256–2260 (1973).

    ADS  CAS  Google Scholar 

  11. Tonegawa, S. & Baldi, I. Biochem. biophys. Res. Commun. 51, 81–87 (1973).

    CAS  PubMed  Google Scholar 

  12. Schechter, I., McKean, D. J., Guyer, R. & Terry, W. Science 188, 160–162 (1975).

    ADS  CAS  PubMed  Google Scholar 

  13. Schechter, I. & Burstein, Y. Biochem. biophys. Res. Commun. 68, 489–496 (1976).

    CAS  PubMed  Google Scholar 

  14. Blobel, G. et al. Symp. Soc. exp. Biol. 33, 9–36 (1979).

    CAS  PubMed  Google Scholar 

  15. Blobel, G. & Dobberstein, B. J. Cell Biol. 67, 835–851 (1975).

    CAS  PubMed  Google Scholar 

  16. Blobel, G. & Dobberstein, B. J. Cell Biol. 67, 852–862 (1975).

    CAS  PubMed  Google Scholar 

  17. Devillers-Thiery, A., Kindt, T., Scheele, G. & Blobel, G. Proc. natn. Acad. Sci. U.S.A. 72, 5016–5020 (1975).

    ADS  CAS  Google Scholar 

  18. Inouye, H. & Beckwith, J. Proc. natn. Acad. Sci. U.S.A. 74, 1440–1444 (1977).

    ADS  CAS  Google Scholar 

  19. Randall, L. L., Hardy, S. J. S. & Josefsson, L.-G. Proc. natn. Acad. Sci. U.S.A. 75, 1209–1212 (1978).

    ADS  CAS  Google Scholar 

  20. Sarvas, M., Hirth, K. P., Fuchs, E. & Simons, K. FEBS Lett. 95, 76–80 (1978).

    CAS  PubMed  Google Scholar 

  21. Sutcliffe, J. G. Proc. natn. Acad. Sci. U.S.A. 75, 3737–3741 (1978).

    ADS  CAS  Google Scholar 

  22. Inouye, S., Wang, S., Kekizawa, J., Halegoua, S. & Inouye, M. Proc. natn. Acad. Sci. U.S.A. 74, 1004–1008 (1977).

    ADS  CAS  Google Scholar 

  23. Lin, J. J. C., Kanazawa, H., Ozols, J. & Wu, H. C. Proc. natn. Acad. Sci. U.S.A. 75, 4891–4895 (1978).

    ADS  CAS  Google Scholar 

  24. Konings, R. N. H., Hulsebos, T. & Van den Hondel, C. A. J. Virol. 15, 570–584 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Sugimoto, K., Sugisaki, H. & Takanami, M. J. molec. Biol. 110, 487–507 (1977).

    Google Scholar 

  26. Chang, C. N., Blobel, G. & Model, P. Proc. natn. Acad. Sci. U.S.A. 75, 361–365 (1978).

    ADS  CAS  Google Scholar 

  27. Lingappa, V. R., Katz, F. N., Lodish, H. F. & Blobel, G. J. biol. Chem. 253, 8667–8670 (1978).

    CAS  PubMed  Google Scholar 

  28. Inouye, M. & Halegoua, S. CRC Crit. Rev. Biochem. (in the press).

  29. Burstein, Y. & Schechter, I. Proc. natn. Acad. Sci. U.S.A. 74, 716–720 (1977).

    ADS  CAS  Google Scholar 

  30. Palmiter, R. D., Gagnon, J., Ericsson, L. H. & Walsh, K. A. J. biol. Chem. 252, 6386–6393 (1977).

    CAS  PubMed  Google Scholar 

  31. Habener, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 75, 2616–2620, (1978).

    ADS  CAS  Google Scholar 

  32. Smith, W. P., Tai, P.-C., Thompson, R. C. & Davis, B. D. Proc. natn. Acad. Sci. U.S.A. 74, 2830–2834 (1977).

    ADS  CAS  Google Scholar 

  33. Bretscher, M. S. J. molec. Biol. 58, 775–781 (1971).

    CAS  PubMed  Google Scholar 

  34. Smith, W. P., Tai, P.-C. & Davis, B. D. Biochemistry 18, 198–202 (1979).

    PubMed  Google Scholar 

  35. Smith, W. P., Tai, P.-C., Murphy, J. R. & Davis, B. D. J. Bact. (in the press).

  36. Leij, L., Kingma, J. & Withold, B. Biochim. biophys. Acta 512, 365–376 (1978).

    PubMed  Google Scholar 

  37. Katz, F. N., Rothman, J. E., Lingappa, V. R., Blobel, G. & Lodish, H. F. Proc. natn. Acad. Sci. U.S.A. 74, 3278–3282 (1977).

    ADS  CAS  Google Scholar 

  38. Rothman, J. E. & Lodish, H. F. Nature 269, 775–780 (1977).

    ADS  CAS  PubMed  Google Scholar 

  39. Cancedda, R. & Schlessinger, M. J. J. Bact. 117, 290–301 (1974).

    CAS  PubMed  Google Scholar 

  40. Randall, L. L. & Hardy, S. J. S. Eur. J. Biochem. 75, 43–53 (1977).

    CAS  PubMed  Google Scholar 

  41. Halegoua, S., Hirashima, A., Sekizawa, J. & Inouye, M. Eur. J. Biochem. 69, 163–167 (1976).

    CAS  PubMed  Google Scholar 

  42. Crane, L. J. & Lampen, J. O. Archs Biochem. Biophys. 160, 655–666 (1974).

    CAS  Google Scholar 

  43. Yamamoto, S. & Lampen, J. O. Proc. natn. Acad. Sci. U.S.A. 73, 1457–1461 (1976).

    ADS  CAS  Google Scholar 

  44. Habener, J. F., Kemper, B., Potts, J. T. Jr & Rich, A. Science 178, 630–633.

  45. Chan, S. J. & Steiner, D. F. Trends biochem. Sci. 2, 254–256 (1977).

    CAS  Google Scholar 

  46. Pappenheimer, Jr., A. M. A. Rev. Biochem. 46, 69–94 (1977).

    CAS  Google Scholar 

  47. Mandel, G. & Wickner, W. Proc. natn. Acad. Sci. U.S.A. 76, 236–240 (1979).

    ADS  CAS  Google Scholar 

  48. Randall, L. L., Josefsson, L.-G. & Hardy, S. J. S. Eur. J. Biochem. 92, 411–415 (1978).

    CAS  PubMed  Google Scholar 

  49. Casadaban, M. J. J. molec. Biol. 104, 541–555 (1976).

    CAS  PubMed  Google Scholar 

  50. Franklin, N. C. A. Rev. Genet. 12, 193–221 (1978).

    CAS  Google Scholar 

  51. Silhavy, T. J., Casadaban, M. J., Shuman, H. A. & Beckwith, J. R. Proc. natn. Acad. Sci. U.S.A. 73, 3423–3427 (1976).

    ADS  CAS  Google Scholar 

  52. Silhavy, T. J., Shuman, H. A., Beckwith, J. & Schwartz, M. Proc. natn. Acad. Sci. U.S.A. 74, 5411–5415 (1977).

    ADS  CAS  Google Scholar 

  53. Bassford, P. & Beckwith, J. Nature 277, 538–541 (1979).

    ADS  CAS  PubMed  Google Scholar 

  54. Silhavy, T. J., Bassford, P. & Beckwith, J. in Bacterial Outer Membranes: Biogenesis and Function (ed. Inouye, M.) (Wiley, New York, 1979).

    Google Scholar 

  55. Emr, S. D., Schwartz, M. & Silhavy, T. J. Proc. natn. Acad Sci. U.S.A. 75, 5802–5806 (1978).

    ADS  CAS  Google Scholar 

  56. Bassford, P. J., Silhavy, T. J. & Beckwith, J. R. J. Bact. 139, 19–31 (1979).

    CAS  PubMed  Google Scholar 

  57. Wanner, B., Sarthy, A. & Beckwith, J. R. J. Bact. 140, 229–239 (1979).

    CAS  PubMed  Google Scholar 

  58. Tai, P.-C., Smith, W. P. & Davis, B. D. in Limited Proteolysis in Microorganisms. Fogarty Conference, National Institutes of Health, 171–175 (US Government Printing Office, Washington, 1978).

    Google Scholar 

  59. Adelman, M. R., Sabatini, D. D. & Blobel, G. J. Cell Biol. 56, 206–229 (1973).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sabatini, D. D. & Kreibich, G. in The Enzymes of Biological Membranes Vol. 2 (ed. Martonosi, A.) 531–579 (Plenum, New York, 1976).

    Google Scholar 

  61. Chua, N.-H., Blobel, G., Siekevitz, P. & Palade, G. E. J. Cell Biol. 71, 497–514 (1976).

    CAS  PubMed  Google Scholar 

  62. Smith, W. P., Tai, P.-C. & Davis, B. D. Proc. natn. Acad. Sci. U.S.A. 75, 814–817 (1978).

    ADS  CAS  Google Scholar 

  63. DiRienzo, J. M., Nakamura, K. & Inouye, M. A. Rev. Biochem. 47, 481–532 (1978).

    CAS  Google Scholar 

  64. Smith, W. P., Tai, P.-C. & Davis, B. D. Proc. natn. Acad. Sci. U.S.A. 75, 5922–5925 (1978).

    ADS  CAS  Google Scholar 

  65. Glenn, A. R. A. Rev. Microbiol. 30, 41–62 (1976).

    CAS  Google Scholar 

  66. Malkin, L. I. & Rich, A. J. molec. Biol. 26, 329–346 (1967).

    CAS  PubMed  Google Scholar 

  67. Blobel, G. & Sabatini, D. D. J. Cell Biol. 45, 130–145 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kreibich, G., Ulrich, B. L. & Sabatini, D. D. J. Cell Biol. 77, 464–487 (1978).

    CAS  PubMed  Google Scholar 

  69. Kreibich, G., Freienstein, C. M., Pereyra, B. N., Ulrich, B. L. & Sabatini, D. D. J. Cell Biol. 77, 488–506 (1978).

    CAS  PubMed  Google Scholar 

  70. Rothman, S. S. Science 190, 747–753 (1975).

    ADS  CAS  PubMed  Google Scholar 

  71. Bretscher, M. S. Science 181, 622–629 (1973).

    ADS  CAS  PubMed  Google Scholar 

  72. Rothman, J. E. & Lenard, J. Science 195, 743–753 (1977).

    ADS  CAS  PubMed  Google Scholar 

  73. Nichols, J. C., Tai, P.-C. & Murphy, J. R. Proc. 15th Joint Conference on Cholera, The U.S.–Japan Cooperative Medical Science Program, 48 (National Institute of Allergy and Infectious Diseases, Bethesda, 1979).

    Google Scholar 

  74. Ito, K., Mandel, G. & Wickner, W. Proc. natn. Acad. Sci. U.S.A. 76, 1199–1203 (1979).

    ADS  CAS  Google Scholar 

  75. Chang, C. N., Model, P. & Blobel, G. Proc. natn. Acad. Sci. U.S.A. 76, 1251–1255 (1979).

    ADS  CAS  Google Scholar 

  76. Dobberstein, B., Blobel, G. & Chua, N.-H. Proc. natn. Acad. Sci. U.S.A. 74, 1082–1085 (1977).

    ADS  CAS  Google Scholar 

  77. Chua, N.-H. & Schmidt, G. W. Proc. natn. Acad. Sci. U.S.A. 75, 6110–6114 (1978).

    ADS  CAS  Google Scholar 

  78. Cashmore, A. R., Broadhurst, M. K. & Gray, R. E. Proc. natn. Acad. Sci. U.S.A. 75, 655–659.

  79. Schmidt, G. W., Devillers-Thiery, A., Desruisseaux, H., Blobel, G. & Chua, N.-H. J. Cell Biol. (in the press).

  80. Highfield, P. E. & Ellis, R. J. Nature 271, 420–424 (1978).

    ADS  CAS  Google Scholar 

  81. Maccecchini, M.-L., Rudin, Y., Blobel, G. & Schatz, G. Proc. natn. Acad. Sci. U.S.A. 76, 343–347 (1979).

    ADS  CAS  Google Scholar 

  82. Poyton, R. O. & McKemmie, E. J. biol. Chem. 254, 6763–6771 (1979).

    CAS  PubMed  Google Scholar 

  83. Poyton, R. O. & McKemmie, E. J. biol. Chem. 254, 6772–6780 (1979).

    CAS  PubMed  Google Scholar 

  84. Wickner, W. A. Rev. Biochem. 48, 23–45 (1979).

    CAS  Google Scholar 

  85. Nelson, N. & Schatz, F. Proc. natn. Acad. Sci. U.S.A. 76, 4365–4369 (1979).

    ADS  CAS  Google Scholar 

  86. Jakes, K. S. & Model, P. J. Bact. 138, 770–778 (1979).

    CAS  PubMed  Google Scholar 

  87. Achtman, M., Manning, P. A., Edelbluth, C. & Herrlich, P. Proc. natn. Acad. Sci. U.S.A. 76, (in the press).

  88. Palmiter, R. D., Gagnon, J. & Walsh, K. A. Proc. natn. Acad. Sci. U.S.A. 75, 94–98 (1978).

    ADS  CAS  Google Scholar 

  89. Goldman, B. M. & Blobel, G. Proc. natn. Acad. Sci. U.S.A. 75, 5066–5070 (1978).

    ADS  CAS  Google Scholar 

  90. Thibodeau, S. N., Palmiter, R. D. & Walsh, K. A. J. biol. Chem. 253, 9018–9023 (1978).

    CAS  PubMed  Google Scholar 

  91. Lingappa, V. R., Shields, D., Woo, S. L. C. & Blobel, G. J. Cell Biol. 79, 567–572 (1978).

    CAS  PubMed  Google Scholar 

  92. Lingappa, V. R., Lingappa, J. R. & Blobel, G. Nature 281, 117–121 (1979).

    ADS  CAS  PubMed  Google Scholar 

  93. Bayer, M. E. J. Virol. 2, 346–356 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Smit, J. & Nikaido, H. J. Bact. 135, 687–702 (1978).

    CAS  Google Scholar 

  95. Ryter, A., Shuman, H. & Schwartz, M. J. Bact. 122, 295–301 (1975).

    CAS  PubMed  Google Scholar 

  96. Shen, B. H. P. & Boos, W. Proc. natn. Acad. Sci. U.S.A. 70, 1481–1485 (1973).

    ADS  CAS  Google Scholar 

  97. Dietzel, I., Kolb, B. & Boos, W. Archs Microbiol. 118, 207–218 (1978).

    CAS  Google Scholar 

  98. Furthmayer, H., Galardy, R. E., Tomita, M. & Marchesi, V. T. Archs Biochem. Biophys. 185, 21–29 (1978).

    Google Scholar 

  99. Waxman, D. J. & Strominger, J. J. biol. Chem. 254, 4863–4875 (1979).

    CAS  PubMed  Google Scholar 

  100. Pages, J. M., Piovant, M., Varenne, S. & Lazdunski, C. Eur. J. Biochem. 86, 589–602 (1978).

    CAS  PubMed  Google Scholar 

  101. Kimura, K. & Izui, K. Biochem. biophys. Res. Commun. 70, 900–906 (1976).

    CAS  PubMed  Google Scholar 

  102. Tribhuwan, R. C. & Pradhan, D. S. J. Bact. 131, 431–437 (1977).

    CAS  PubMed  Google Scholar 

  103. Villa-Komaroff, L. et al. Proc. natn. Acad. Sci. U.S.A. 75, 3727–3731 (1978).

    ADS  CAS  Google Scholar 

  104. Fraser, T. & Bruce, B. J. Proc. natn. Acad. Sci. U.S.A. 75, 5936–5940 (1978).

    ADS  CAS  Google Scholar 

  105. Mercereau-Puijalon, O. et al. Nature 275, 505–513 (1978).

    ADS  CAS  Google Scholar 

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  1. Bacterial Physiology Unit, Harvard Medical School, Boston, Massachusetts, 02115

    Bernard D. Davis & Phang-C. Tai

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Davis, B., Tai, PC. The mechanism of protein secretion across membranes. Nature 283, 433–438 (1980). https://doi.org/10.1038/283433a0

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