Signals and components involved in the translocation of proteins across the endoplasmic reticulum membrane

  • Tom A. Rapoport
Conference paper
Part of the NATO ASI Series book series (volume 40)


The endoplasmic reticulum (ER) is a major site of protein translocation in eukaryotic cells. Secretory proteins, lysosomal enzymes, lumenal proteins of the ER, plasma membrane proteins, integral ER membrane proteins, to name a few classes which have been studied extensively, are all translocated across or inserted into the ER membrane. Signals contained in the protein sequence target the protein to the ER and determine whether or not it is integrated in the membrane. The present review summarizes our current knowledge on some aspects of these problems, with special emphasis on the work carried out in our laboratory.


Signal Sequence Endoplasmic Reticulum Membrane Protein Translocation Signal Recognition Particle Nascent Polypeptide Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Austen, B.M. and Ridd, D.H. (1983) Studies on the binding of a signal peptide to pancreatic rough microsomal membranes. Biochem. Soc. Trans. 11: 160Google Scholar
  2. Baker, R.K. and Lively, M.O. (1987) Purification and characterization of hen oviduct microsomal signal peptidase. Biochemistry 26: 8561–8567PubMedCrossRefGoogle Scholar
  3. Bendzko, P., Prehn, S., Pfeil, W. and Rapoport, T.A. (1982) Different modes of membrane interactions of the signal sequence of carp preproinsulin and of the insertion sequence of rabbit cytochrome b5. Eur. J. Biochem. 123: 121PubMedCrossRefGoogle Scholar
  4. Blobel, G. and Sabatini, D. (1971) Ribosome-membrane interaction in eukaryotic cells. In: Manson, L. A. (Ced) Biomembranes. Plenum Press, New York, p. 193Google Scholar
  5. Blobel, G. and Dobberstein, B. (1975) Transfer of proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J. Cell Biol. 67: 852–862PubMedCrossRefGoogle Scholar
  6. Blobel, G. (1980) Intracellular protein topogenesis. Proc. Natl. Acad. Sci. USA 77: 1496–1500PubMedCrossRefGoogle Scholar
  7. Chirico, W.J., Waters, M.G. and Blobel, G. (1988) 70K heat shock related proteins stimulate protein translocation into microsomes. Nature 332: 805–810PubMedCrossRefGoogle Scholar
  8. Connolly, T. and Gilmore, R. (1989) The signal recognition particle receptor mediates the GTP-dependent displacement of SRP from the signal sequence of the nascent polypeptide. Cell, in pressGoogle Scholar
  9. Deshaies, R.J. and Schekman, R. (1987) A yeast mutant defective at an early stage in import of secretory protein precursors in tothe endoplasmic reticulum. J. Cell Biol. 105: 633–645PubMedCrossRefGoogle Scholar
  10. Deshaies, R.J., Koch, B.D., Werner-Washburne, M., Craig, E.A. and Schekman, R. (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332: 800–805PubMedCrossRefGoogle Scholar
  11. Emr, S.D., Hanley-Way, S. and Silhavy, T.J. (1981) Suppressor mutations that restore export of a protein with a defective signal sequence. Cell 23: 79–88PubMedCrossRefGoogle Scholar
  12. Engelmann, D.M. and Steitz T. A. (1981) The spontaneous insertion of proteins into and across membranes: The helical hairpin hypothesis. Cell 23: 411–422Google Scholar
  13. Evans, E.A., Gilmore, R. and Blobel, G. (1986) Purification of microsomal signal peptidase as a complex. Proc. Natl. Acad. Sci. USA 83: 581–585PubMedCrossRefGoogle Scholar
  14. Finkelstein, A.V., Bendzko, P. and Rapoport, T.A. (1983) Recognition of signal sequences. FEBS Lett. 161: 176PubMedCrossRefGoogle Scholar
  15. Gilmore, R., Walter, P. and Blobel, G. (1982) Protein translocation across the endoplasmic reticulum. II. Isolation and characterization of the signal recognition particle receptor. J. Cell Biol. 95: 470–477PubMedCrossRefGoogle Scholar
  16. Gilmore, R. and Blobel, G. (1983) Transient involvement of signal recognition particle and its receptor in the microsomal membrane prior to protein translocation. Cell 35: 677–685PubMedCrossRefGoogle Scholar
  17. Hansen, W., Garcia, P.D. and Walter, P. (1986) in vitro protein translocation across the yeast endoplasmic reticulum: ATP-dependent posttranslational translocation of the prepro- alpha-factor. Cell 45: 397–406PubMedCrossRefGoogle Scholar
  18. Hartmann, E., Wiedmann, M. and Rapoport, T.A. (1989b) A membrane component of the endoplasmic reticulum that may be essential for protein translocation. EMBO-J. in pressGoogle Scholar
  19. Hartmann, E., Rapoport, T. A. and Lodish, H.F. (1989a) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc. Natl. Acad. Sci. USA, in pressGoogle Scholar
  20. von Heijne, G. and Blomberg, C. (1979) Transmembrane translocation of proteins: The direct transfer model. Eur. J. Biochem. 97: 175–181Google Scholar
  21. von Heijne, G. (1985) Structural and thermodynamic aspects of the transfer of proteins into and across membranes. Curr. Top. in Membr. and Transp., 24: 151–179Google Scholar
  22. Hortsch, M., Avossa, D. and Meyer, D.I. (1986) Characterization of secretory protein translocation: ribosome-membrane interaction in endoplasmic reticulum. J. Cell Biol. 103: 241–253PubMedCrossRefGoogle Scholar
  23. Kreibich, G., Czako-Graham, M., Grebenau, R., Mok, W., Rodriguez-Boulan, E. and Sabatini, D.D. (1978) Characterization of the ribosomal binding site in rat liver rough microsomes: ribophorins I and II, two integral membrane proteins related to ribosome binding. J. Supramolec. Structure 8: 279–302CrossRefGoogle Scholar
  24. Krieg, U.C., Walter, P. and Johnson, A. E. (1986) Photocrosslinking of the signal sequence of nascent preprolactin of the 54-kilodalton polypeptide of the signal recognition particle. Proc. Natl. Acad. Sci. USA 83: 8604–8608PubMedCrossRefGoogle Scholar
  25. Kurzchalia, T.V., Wiedmann, M., Girshovich, A.S., Bochkareva, E.S., Bielka, H. and Rapoport, T.A. (1986) The signal sequence of nascent preprolactin interacts with the 54K polypeptide of the signal recognition particle. Nature 320: 634–636PubMedCrossRefGoogle Scholar
  26. Meyer, D.I., Krause, E. and Dobberstein, B. (1982) Secretory protein translocation across membranes — the role of the docking protein. Nature 297: 647–650PubMedCrossRefGoogle Scholar
  27. Prehn, S., Tsamaloukas, A. and Rapoport, T. A. (1980) Demonstration of specific receptors of the rough endoplasmic membrane for the signal sequence of carp preproinsulin. Eur. J. Biochem. 107: 185–195PubMedCrossRefGoogle Scholar
  28. Rapoport, T. A. (1986) Protein translocation across and integration into membranes. CRC Crit. Rev. Biochem. 20: 73–137CrossRefGoogle Scholar
  29. Rapoport, T.A., Wiedmann, M., Kurzchalia, T.V. and Hartmann, E. (1989) Signal recognition in protein translocation across the endoplasmic reticulum membrane. Biochem. Soc. Trans. 17: 325–328PubMedGoogle Scholar
  30. Rothblatt, J.A. and Meyer, D.I. (1986) Secretion in yeast: reconstitution of the translocation and glycosylation of alpha-factor and invertase in a homologous cell-free system. Cell 44: 619–628PubMedCrossRefGoogle Scholar
  31. Schlenstedt, G. and Zimmermann, R. (1987) Import of frog prepropeptide Gla into microsomes requires ATP but does not involve doking protein or ribosomes. EMBO-J. 6: 699–703PubMedGoogle Scholar
  32. Siegel, V. and Walter, P. (1985) Elongation arrest is not a prerequisite for secretory protein translocation across the microsomal membrane. J. Cell Biol. 100: 1913–1921PubMedCrossRefGoogle Scholar
  33. Siegel, V. and Walter, P. (1988) Each of the activities of signal recognition particle (SRP) is contained within a distinct domain: analysis of biochemical mutants of SRP. Cell 52: 39–49PubMedCrossRefGoogle Scholar
  34. Tajima, S., Lauffer, L., Rath, V.L. and Walter, P. (1986) The signal recognition particle receptor is a complex that contains two distinct polypeptide chains. J. Cell Biol. 103: 1167–1178PubMedCrossRefGoogle Scholar
  35. Walter, P. and Blobel, G. (1981) Translocation of proteins across the endoplasmic reticulum. III. Signal recognition protein (SRP) causes signal sequence — dependent and site-specific arrest of chain elongation that is released by microsomal membranes. J. Cell Biol. 91: 557–561PubMedCrossRefGoogle Scholar
  36. Walter, P. and Blobel, G. (1982) Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum membrane. Nature 299: 691PubMedCrossRefGoogle Scholar
  37. Walter, P. and Lingappa, V.R. (1986) Mechanism of protein translocation across the endoplasmic reticulum membrane. Ann. Rev. Cell Biol. 2: 499–516PubMedCrossRefGoogle Scholar
  38. Waters, M.G. and Blobel, G. (1986) Secretory protein translocation in a yeast cell free system can occur posttranslationally and requires ATP hydrolysis. J. Cell Biol. 102: 1543–1550PubMedCrossRefGoogle Scholar
  39. Wessels, H.P. and Spiess, M. (1988) Insertion of a multi- spanning membrane protein occurs sequentially and requires only one signal sequence. Cell 55: 61–70PubMedCrossRefGoogle Scholar
  40. Wiedmann, M., Kurzchalia, T.V., Bielka, H. and Rapoport, T.A. (1987a) Direct probing of the interaction between the signal sequence of nascent preprolactin and the signal recognition particle by specific crosslinking. J. Cell Biol. 104: 201–208PubMedCrossRefGoogle Scholar
  41. Wiedmann, M., Wiedmann, B., Voigt, S., Wachter, E., Mueller, H.-G. and Rapoport, T.A. (1988b) Post-translational transport of proteins into microsomal membranes of Candida maltosa. EMBO-J. 7: 1763–1768PubMedGoogle Scholar
  42. Wiedmann, M., Kurzchalia, T.V., Hartmann, E. and Rapoport, T.A. (1987c) A signal sequence receptor in the endoplasmic reticulum membrane. Nature 328: 830–833PubMedCrossRefGoogle Scholar
  43. Wiedmann, M., Goerlich, D., Kurzchalia, T.V. and Rapoport, T.A. (1989) Probing by photocrosslinking the environment of nascent preprolactin during its translocation across the endoplasmic reticulum membrane. Submitted for publication.Google Scholar
  44. YaDeau, J. and Blobel, G. (1989) Solubilization and characterization of yeast signal peptidase. J. Biol. Chem. 264: 2928–2934PubMedGoogle Scholar
  45. Yu, Y.H., Sabatini, D.D. and Kreibich, G. (1988) Antibodies against ribophorin I inhibit the translocation activity of rough microsomal membranes. J. Cell Biol. 107: 766aGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • Tom A. Rapoport
    • 1
  1. 1.Central Institute of Molecular BiologyAcademy of Sciences of the GDRBerlin-BuchGermany

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