1887

Abstract

Yellow fever virus (YFV) encodes two envelope proteins, pre-membrane (prM) and envelope (E), that accumulate in the endoplasmic reticulum (ER). The C termini of prM and E form two antiparallel transmembrane -helices that contain ER-retention signals. To understand further the ER retention of the prME heterodimer, we characterized the subcellular localization of chimeric proteins made of a reporter protein fused to the transmembrane segments of YFV envelope proteins. We showed that at least three of the transmembrane segments of the prME heterodimer are ER-retention signals. Interestingly, increasing the length of these -helices led to the export of the chimeric proteins out of the ER. Furthermore, adding a diacidic export signal at the C terminus of the first transmembrane segment of the E protein also induced export to the cell surface. However, adding this export signal at the C terminus of the first transmembrane segment of E in the context of prME did not change the subcellular localization of the prME heterodimer, suggesting the presence of a stronger ER-retention signal outside the first transmembrane segment of E. Importantly, the diacidic export motif added to the C terminus of the first transmembrane segment of the prM protein was not sufficient to export a chimeric protein out of the ER, indicating that this sequence is a dominant ER-retention signal. Together, these data indicate that a combination of several signals of different strengths contributes to the ER retention of the YFV envelope protein heterodimer.

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2010-02-01
2021-10-24
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References

  1. Allison, S. L., Stadler, K., Mandl, C. W., Kunz, C. & Heinz, F. X.(1995). Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form. J Virol 69, 5816–5820. [Google Scholar]
  2. Allison, S. L., Stiasny, K., Stadler, K., Mandl, C. W. & Heinz, F. X.(1999). Mapping of functional elements in the stem-anchor region of tick-borne encephalitis virus envelope protein E. J Virol 73, 5605–5612. [Google Scholar]
  3. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, A. D., Seidman, J. G., Smith, J. A. & Struhl, K. (editors)(2000).Current Protocols in Molecular Biology. New York: Wiley.
  4. Belouzard, S., Delcroix, D. & Rouille, Y.(2004). Low levels of expression of leptin receptor at the cell surface result from constitutive endocytosis and intracellular retention in the biosynthetic pathway. J Biol Chem 279, 28499–28508.[CrossRef] [Google Scholar]
  5. Bretscher, M. S. & Munro, S.(1993). Cholesterol and Golgi apparatus. Science 261, 1280–1281.[CrossRef] [Google Scholar]
  6. Cocquerel, L., Wychowski, C., Minner, F., Penin, F. & Dubuisson, J.(2000). Charged residues in the transmembrane domains of hepatitis C virus glycoproteins play a key role in the processing, subcellular localization and assembly of these envelope proteins. J Virol 74, 3623–3633.[CrossRef] [Google Scholar]
  7. Cocquerel, L., Op de Beeck, A., Lambot, M., Roussel, J., Delgrange, D., Pillez, A., Wychowski, C., Penin, F. & Dubuisson, J.(2002). Topologic changes in the transmembrane domains of hepatitis C virus envelope glycoproteins. EMBO J 21, 2893–2902.[CrossRef] [Google Scholar]
  8. Cole, N. B., Sciaky, N., Marotta, A., Song, J. & Lippincott-Schwartz, J.(1996). Golgi dispersal during microtubule disruption: regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites. Mol Biol Cell 7, 631–650.[CrossRef] [Google Scholar]
  9. Despres, P., Cahour, A., Dupuy, A., Deubel, V., Bouloy, M., Digoutte, J. P. & Girard, M.(1987). High genetic stability of the region coding for the structural proteins of yellow fever virus strain 17D. J Gen Virol 68, 2245–2247.[CrossRef] [Google Scholar]
  10. Heinz, F. X. & Allison, S. L.(2000). Structures and mechanisms in flavivirus fusion. Adv Virus Res 55, 231–269. [Google Scholar]
  11. Hsieh, S. C., Liu, I. J., King, C. C., Chang, G. J. & Wang, W. K.(2008). A strong endoplasmic reticulum retention signal in the stem-anchor region of envelope glycoprotein of dengue virus type 2 affects the production of virus-like particles. Virology 374, 338–350.[CrossRef] [Google Scholar]
  12. Konishi, E. & Mason, P. W.(1993). Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol 67, 1672–1675. [Google Scholar]
  13. Kuhn, R. J., Zhang, W., Rossmann, M. G., Pletnev, S. V., Corver, J., Lenches, E., Jones, C. T., Mukhopadhyay, S., Chipman, P. R. & other authors(2002). Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108, 717–725.[CrossRef] [Google Scholar]
  14. Lemmon, M. A., MacKenzie, K. R., Arkin, I. T. & Engelman, D. M.(1997). Transmembrane α-helix interactions in folding and oligomerization of integral membrane proteins. In Membrane Protein Assembly, pp. 3–23. Edited by G. von Heijne. Heidelberg: Springer.
  15. Lewis, M. J. & Pelham, H. R. B.(1992). Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell 68, 353–364.[CrossRef] [Google Scholar]
  16. Lindenbach, B. D., Thiel, H. J. & Rice, C. M.(2007).Flaviviridae: the viruses and their replication. In Fields Virology, 5th edn, pp. 1101–1152. Edited by D. M. Knipe & P. M. Howley. Philadelphia, PA: Lippincott Williams & Wilkins.
  17. Lorenz, I. C., Kartenbeck, J., Mezzacasa, A., Allison, S. L., Heinz, F. X. & Helenius, A.(2003). Intracellular assembly and secretion of recombinant subviral particles from tick-borne encephalitis virus. J Virol 77, 4370–4382.[CrossRef] [Google Scholar]
  18. Mackenzie, J. M. & Westaway, E. G.(2001). Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75, 10787–10799.[CrossRef] [Google Scholar]
  19. Martire, G., Mottola, G., Pascale, M. C., Malagolini, N., Turrini, I., Serafini-Cessi, F., Jackson, M. R. & Bonatti, S.(1996). Different fate of a single reporter protein containing KDEL or KKXX targeting signals stably expressed in mammalian cells. J Biol Chem 271, 3541–3547.[CrossRef] [Google Scholar]
  20. Nishimura, N. & Balch, W. E.(1997). A di-acidic signal required for selective export from the endoplasmic reticulum. Science 277, 556–558.[CrossRef] [Google Scholar]
  21. Op De Beeck, A., Molenkamp, R., Caron, M., Ben Younes, A., Bredenbeek, P. & Dubuisson, J.(2003). Role of the transmembrane domains of prM and E proteins in the formation of yellow fever virus envelope. J Virol 77, 813–820.[CrossRef] [Google Scholar]
  22. Op De Beeck, A., Rouillé, Y., Caron, M., Duvet, S. & Dubuisson, J.(2004). The transmembrane domains of prM and E proteins of yellow fever virus are ER localization signals. J Virol 78, 12591–12602.[CrossRef] [Google Scholar]
  23. Pedrazzini, E., Villa, A. & Borgese, N.(1996). A mutant cytochrome b5 with a lengthened membrane anchor escapes from the endoplasmic reticulum and reaches the plasma membrane. Proc Natl Acad Sci U S A 93, 4207–4212.[CrossRef] [Google Scholar]
  24. Ronchi, P., Colombo, S., Francolini, M. & Borgese, N.(2008). Transmembrane domain-dependent partitioning of membrane proteins within the endoplasmic reticulum. J Cell Biol 181, 105–118.[CrossRef] [Google Scholar]
  25. Rouillé, Y., Helle, F., Delgrange, D., Roingeard, P., Voisset, C., Blanchard, E., Belouzard, S., McKeating, J., Patel, A. H. & other authors(2006). Subcellular localization of hepatitis C virus structural proteins in a cell culture system that efficiently replicates the virus. J Virol 80, 2832–2841.[CrossRef] [Google Scholar]
  26. Sambrook, J., Fritsch, E. F. & Maniatis, T.(1989).Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  27. Saraste, J. & Svensson, K.(1991). Distribution of the intermediate elements operating in ER to Golgi transport. J Cell Sci 100, 415–430. [Google Scholar]
  28. Schweizer, A., Fransen, J. A. M., Bächi, T., Ginsel, L. & Hauri, H.-P.(1988). Identification, by a monoclonal antibody, of a 53-kD protein associated with tubulo-vesicular compartment at the cis-side of the Golgi apparatus. J Cell Biol 107, 1643–1653.[CrossRef] [Google Scholar]
  29. Sevier, C. S., Weisz, O. A., Davis, M. & Machamer, C. E.(2000). Efficient export of the vesicular stomatitis virus G protein from the endoplasmic reticulum requires a signal in the cytoplasmic tail that includes both tyrosine-based and di-acidic motifs. Mol Biol Cell 11, 13–22.[CrossRef] [Google Scholar]
  30. Shenkman, M., Ayalon, M. & Lederkremer, G. Z.(1997). Endoplasmic reticulum quality control of asialoglycoprotein receptor H2a involves determinant for retention and not retrieval. Proc Natl Acad Sci U S A 94, 11363–11368.[CrossRef] [Google Scholar]
  31. Szczesna-Skorupa, E. & Kemper, B.(2000). Endoplasmic reticulum retention determinants in the transmembrane and linker domains of cytochrome P450 2C1. J Biol Chem 275, 19409–19415.[CrossRef] [Google Scholar]
  32. Townsley, F. M., Wilson, D. W. & Pelham, H. R. B.(1993). Mutational analysis of the human KDEL receptor: distinct structural requirements for Golgi retention, ligand binding and retrograde transport. EMBO J 12, 2821–2829. [Google Scholar]
  33. Wengler, G.(1989). Cell-associated West Nile flavivirus is covered with E+pre-M protein heterodimers which are destroyed and reorganized by proteolytic cleavage during virus release. J Virol 63, 2521–2526. [Google Scholar]
  34. Yang, M., Ellenberg, J., Bonifacino, J. S. & Weissman, A. M.(1997). The transmembrane domain of a carboxy-terminal anchored protein determines localization to the endoplasmic reticulum. J Biol Chem 272, 1970–1975.[CrossRef] [Google Scholar]
  35. Zhang, W., Chipman, P. R., Corver, J., Johnson, P. R., Zhang, Y., Mukhopadhyay, S., Baker, T. S., Strauss, J. H., Rossmann, M. G. & Kuhn, R. J.(2003a). Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol 10, 907–912.[CrossRef] [Google Scholar]
  36. Zhang, Y., Corver, J., Chipman, P. R., Zhang, W., Pletnev, S. V., Sedlak, D., Baker, T. S., Strauss, J. H., Kuhn, R. J. & Rossmann, M. G.(2003b). Structures of immature flavivirus particles. EMBO J 22, 2604–2613.[CrossRef] [Google Scholar]
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