1887

Abstract

The rotavirus genome encodes two glycoproteins, one structural (VP7) and one non-structural (NSP4), both of which mature and remain in the endoplasmic reticulum (ER). While three amino acids in the N terminus have been proposed to function as a retention signal for VP7, no information is yet available on how NSP4 remains associated with the ER. In this study, we have investigated the ER retention motif of NSP4 by producing various C-terminal truncations. Deleting the C terminus by 52 amino acids did not change the intracellular distribution of NSP4, but an additional deletion of 38 amino acids diminished the ER retention and resulted in the expression of NSP4 on the cell surface. Brefeldin A treatment prevented NSP4 from reaching the cell surface, suggesting that C-terminal truncated plasma membrane NSP4 is transported through the normal secretory pathway. On the basis of these results, we propose that the region between amino acids 85 and 123 in the cytoplasmic region of NSP4 are involved in ER retention.

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2003-04-01
2019-10-21
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References

  1. Andersson, A. M. & Pettersson, R. F. ( 1998; ). Targeting of a short peptide derived from the cytoplasmic tail of the G1 membrane glycoprotein of Uukuniemi virus (Bunyaviridae) to the Golgi complex. J Virol 72, 9585–9596.
    [Google Scholar]
  2. Au, K. S., Chan, W. K., Burns, J. W. & Estes, M. K. ( 1989; ). Receptor activity of rotavirus nonstructural glycoprotein NS28. J Virol 63, 4553–4562.
    [Google Scholar]
  3. Ball, J. M., Tian, P., Zeng, C. Q., Morris, A. P. & Estes, M. K. ( 1996; ). Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein [see comments]. Science 272, 101–104.[CrossRef]
    [Google Scholar]
  4. Bellamy, A. R. & Both, G. W. ( 1990; ). Molecular biology of rotaviruses. Adv Virus Res 38, 1–43.
    [Google Scholar]
  5. Berglund, P., Sjoberg, M., Garoff, H., Atkins, G. J., Sheahan, B. J. & Liljestrom, P. ( 1993; ). Semliki Forest virus expression system: production of conditionally infectious recombinant particles. Biotechnology 11, 916–920.[CrossRef]
    [Google Scholar]
  6. Bergmann, C. C., Maass, D., Poruchynsky, M. S., Atkinson, P. H. & Bellamy, A. R. ( 1989; ). Topology of the non-structural rotavirus receptor glycoprotein NS28 in the rough endoplasmic reticulum. EMBO J 8, 1695–1703.
    [Google Scholar]
  7. Chan, W. K., Au, K. S. & Estes, M. K. ( 1988; ). Topography of the simian rotavirus nonstructural glycoprotein (NS28) in the endoplasmic reticulum membrane. Virology 164, 435–442.[CrossRef]
    [Google Scholar]
  8. Chen, S. Y., Matsuoka, Y. & Compans, R. W. ( 1991; ). Assembly and polarized release of Punta Toro virus and effects of brefeldin A. J Virol 65, 1427–1439.
    [Google Scholar]
  9. Cocquerel, L., Meunier, J. C., Pillez, A., Wychowski, C. & Dubuisson, J. ( 1998; ). A retention signal necessary and sufficient for endoplasmic reticulum localization maps to the transmembrane domain of hepatitis C virus glycoprotein E2. J Virol 72, 2183–2191.
    [Google Scholar]
  10. Cocquerel, L., Duvet, S., Meunier, J. C., Pillez, A., Cacan, R., Wychowski, C. & Dubuisson, J. ( 1999; ). The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum. J Virol 73, 2641–2649.
    [Google Scholar]
  11. Estes, M. K. & Cohen, J. ( 1989; ). Rotavirus gene structure and function. Microbiol Rev 53, 410–449.
    [Google Scholar]
  12. Jackson, M. R., Nilsson, T. & Peterson, P. A. ( 1990; ). Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum. EMBO J 9, 3153–3162.
    [Google Scholar]
  13. Jackson, M. R., Nilsson, T. & Peterson, P. A. ( 1993; ). Retrieval of transmembrane proteins to the endoplasmic reticulum. J Cell Biol 121, 317–333.[CrossRef]
    [Google Scholar]
  14. Jourdan, N., Maurice, M., Delautier, D., Quero, A. M., Servin, A. L. & Trugnan, G. ( 1997; ). Rotavirus is released from the apical surface of cultured human intestinal cells through nonconventional vesicular transport that bypasses the Golgi apparatus. J Virol 71, 8268–8278.
    [Google Scholar]
  15. Kantanen, M. L., Leinikki, P. & Kuismanen, E. ( 1995; ). Endoproteolytic cleavage of HIV-1 gp160 envelope precursor occurs after exit from the trans-Golgi network (TGN). Arch Virol 140, 1441–1449.[CrossRef]
    [Google Scholar]
  16. Lewis, M. J. & Pelham, H. R. ( 1992; ). Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell 68, 353–364.[CrossRef]
    [Google Scholar]
  17. Mallabiabarrena, A., Jimenez, M. A., Rico, M. & Alarcon, B. ( 1995; ). A tyrosine-containing motif mediates ER retention of CD3-epsilon and adopts a helix-turn structure. EMBO J 14, 2257–2268.
    [Google Scholar]
  18. Mass, D. R. & Atkinson, P. H. ( 1994; ). Retention by the endoplasmic reticulum of rotavirus VP7 is controlled by three adjacent amino-terminal residues. J Virol 68, 366–378.
    [Google Scholar]
  19. Mirazimi, A. & Svensson, L. ( 1998; ). Carbohydrates facilitate correct disulfide bond formation and folding of rotavirus VP7. J Virol 72, 3887–3892.
    [Google Scholar]
  20. Mirazimi, A. & Svensson, L. ( 2000; ). ATP is required for correct folding and disulfide bond formation and folding of rotavirus VP7. J Virol 74, 8048–8052.[CrossRef]
    [Google Scholar]
  21. Mirazimi, A., von Bonsdorff, C. H. & Svensson, L. ( 1996; ). Effect of brefeldin A on rotavirus assembly and oligosaccharide processing. Virology 217, 554–563.[CrossRef]
    [Google Scholar]
  22. Mirazimi, A., Nilsson, M. & Svensson, L. ( 1998; ). The molecular chaperone calnexin interacts with the NSP4 enterotoxin of rotavirus in vivo and in vitro. J Virol 72, 8705–8709.
    [Google Scholar]
  23. Munro, S. & Pelham, H. R. ( 1987; ). A C-terminal signal prevents secretion of luminal ER proteins. Cell 48, 899–907.[CrossRef]
    [Google Scholar]
  24. Newton, K., Meyer, J. C., Bellamy, A. R. & Taylor, J. A. ( 1997; ). Rotavirus nonstructural glycoprotein NSP4 alters plasma membrane permeability in mammalian cells. J Virol 71, 9458–9465.
    [Google Scholar]
  25. Nilsson, T. & Warren, G. ( 1994; ). Retention and retrieval in the endoplasmic reticulum and the Golgi apparatus. Curr Opin Cell Biol 6, 517–521.[CrossRef]
    [Google Scholar]
  26. Nilsson, M., von Bonsdorff, C. H., Weclewicz, K., Cohen, J. & Svensson, L. ( 1998; ). Assembly of viroplasm and virus-like particles of rotavirus by a Semliki Forest virus replicon. Virology 242, 255–265.[CrossRef]
    [Google Scholar]
  27. Nilsson, T., Jackson, M. & Peterson, P. A. ( 1989; ). Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulum. Cell 58, 707–718.[CrossRef]
    [Google Scholar]
  28. Nuchtern, J. G., Bonifacino, J. S., Biddison, W. E. & Klausner, R. D. ( 1989; ). Brefeldin A implicates egress from endoplasmic reticulum in class I restricted antigen presentation. Nature 339, 223–226.[CrossRef]
    [Google Scholar]
  29. Paabo, S., Bhat, B. M., Wold, W. S. & Peterson, P. A. ( 1987; ). A short sequence in the COOH-terminus makes an adenovirus membrane glycoprotein a resident of the endoplasmic reticulum. Cell 50, 311–317.[CrossRef]
    [Google Scholar]
  30. Pelham, H. R. ( 1988; ). Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J 7, 913–918.
    [Google Scholar]
  31. Pelham, H. R. ( 1991; ). Recycling of proteins between the endoplasmic reticulum and Golgi complex. Curr Opin Cell Biol 3, 585–591.[CrossRef]
    [Google Scholar]
  32. Pelham, H. R. ( 1994; ). About turn for the COPs? Cell 79, 1125–1127.[CrossRef]
    [Google Scholar]
  33. Petrie, B. L. ( 1983; ). Biological activity of rotavirus particles lacking glycosylated proteins. In Double-stranded RNA Viruses, pp. 145–156. Edited by R. W. Compans & D. H. L. Bishop. New York: Elsevier.
  34. Pettersson, R. F. ( 1991; ). Protein localization and virus assembly at intracellular membranes. Curr Top Microbiol Immunol 170, 67–106.
    [Google Scholar]
  35. Poruchynsky, M. S., Tyndall, C., Both, G. W., Sato, F., Bellamy, A. R. & Atkinson, P. H. ( 1985; ). Deletions into an NH2-terminal hydrophobic domain result in secretion of rotavirus VP7, a resident endoplasmic reticulum membrane glycoprotein. J Cell Biol 101, 2199–2209.[CrossRef]
    [Google Scholar]
  36. Poruchynsky, M. S., Maass, D. R. & Atkinson, P. H. ( 1991; ). Calcium depletion blocks the maturation of rotavirus by altering the oligomerization of virus-encoded proteins in the ER. J Cell Biol 114, 651–656.[CrossRef]
    [Google Scholar]
  37. Ruggeri, F., Johansen, K., Basile, G., Kraehenbuhl, J.-P. & Svensson, L. ( 1998; ). Antirotavirus immunoglobulin A neutralizes virus in vitro after transcytosis through epithelial cells and protects infant mice from diarrhea. J Virol 72, 2708–2714.
    [Google Scholar]
  38. Schutze, M. P., Peterson, P. A. & Jackson, M. R. ( 1994; ). An N-terminal double-arginine motif maintains type II membrane proteins in the endoplasmic reticulum. EMBO J 13, 1696–1705.
    [Google Scholar]
  39. Svensson, L., Dormitzer, P. R., von Bonsdorff, C. H., Maunula, L. & Greenberg, H. B. ( 1994; ). Intracellular manipulation of disulfide bond formation in rotavirus proteins during assembly. J Virol 68, 5204–5215.
    [Google Scholar]
  40. Tafazoli, F., Zeng, C. Q., Estes, M. K., Magnusson, K. E. & Svensson, L. ( 2001; ). NSP4 enterotoxin of rotavirus induces paracellular leakage in polarized epithelial cells. J Virol 75, 1540–1546.[CrossRef]
    [Google Scholar]
  41. Taylor, J. A., O'Brien, J. A. & Yeager, M. ( 1996; ). The cytoplasmic tail of NSP4, the endoplasmic reticulum-localized non-structural glycoprotein of rotavirus, contains distinct virus binding and coiled coil domains. EMBO J 15, 4469–4476.
    [Google Scholar]
  42. Tian, P., Estes, M. K., Hu, Y., Ball, J. M., Zeng, C. Q. & Schilling, W. P. ( 1995; ). The rotavirus nonstructural glycoprotein NSP4 mobilizes Ca2+ from the endoplasmic reticulum. J Virol 69, 5763–5772.
    [Google Scholar]
  43. Townsley, F. M. & Pelham, H. R. ( 1994; ). The KKXX signal mediates retrieval of membrane proteins from the Golgi to the ER in yeast. Eur J Cell Biol 64, 211–216.
    [Google Scholar]
  44. Weclewicz, K., Kristensson, K., Greenberg, H. B. & Svensson, L. ( 1993a; ). The endoplasmic reticulum-associated VP7 of rotavirus is targeted to axons and dendrites in polarized neurons. J Neurocytol 22, 616–626.[CrossRef]
    [Google Scholar]
  45. Weclewicz, K., Svensson, L., Billger, M., Holmberg, K., Wallin, M. & Kristensson, K. ( 1993b; ). Microtubule-associated protein 2 appears in axons of cultured dorsal root ganglia and spinal cord neurons after rotavirus infection. J Neurosci Res 36, 173–182.[CrossRef]
    [Google Scholar]
  46. Xu, A., Bellamy, A. R. & Taylor, J. A. ( 2000; ). Immobilization of the early secretory pathway by a virus glycoprotein that binds to microtubules. EMBO J 19, 6465–6474.[CrossRef]
    [Google Scholar]
  47. Zhang, M., Zeng, C. Q., Morris, A. P. & Estes, M. K. ( 2000; ). A functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells. J Virol 74, 11663–11670.[CrossRef]
    [Google Scholar]
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