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. 1996 Oct;70(10):6563–6575. doi: 10.1128/jvi.70.10.6563-6575.1996

Targeting of glycoprotein I (gE) of varicella-zoster virus to the trans-Golgi network by an AYRV sequence and an acidic amino acid-rich patch in the cytosolic domain of the molecule.

Z Zhu 1, Y Hao 1, M D Gershon 1, R T Ambron 1, A A Gershon 1
PMCID: PMC190697  PMID: 8794291

Abstract

Previous studies suggested that varicella-zoster virus (VZV) envelope glycoproteins (gps) are selectively transported to the trans-Golgi network (TGN) and that the cytosolic domain of gpI (gE) targets it to the TGN. To identify targeting signals in the gpI cytosolic domain, intracellular protein trafficking was studied in transfected cells expressing chimeric proteins in which a full-length or mutated gpI cytosolic domain was fused to the gpI transmembrane domain and interleukin-2 receptor (tac) ectodomain. Expressed protein was visualized with antibodies to tac. A targeting sequence (AYRV) and a second, acidic amino acid-rich region of the gpI cytosolic domain (putative signal patch) were each sufficient to cause expressed protein to colocalize with TGN markers. This targeting was lost when the tyrosine of the AYRV sequence was replaced with glycine or lysine, when arginine was replaced with glutamic acid, or when valine was substituted with lysine. In contrast, tyrosine could be replaced by phenylalanine and valine could be substituted with leucine. Mutation of alanine to aspartic acid or deletion of alanine abolished TGN targeting. Exposure of transfected cells to antibodies to the tac ectodomain revealed that the TCN targeting of expressed tac-gpI chimeric proteins occurred as a result of selective retrieval from the plasmalemma. These data suggest that the AYRV sequence and a second signaling patch in the cytosolic domain of gpI are responsible for its targeting to the TGN. The observations also support the hypothesis that the TGN plays a critical role in the envelopment of VZV.

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Selected References

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  1. Bos K., Wraight C., Stanley K. K. TGN38 is maintained in the trans-Golgi network by a tyrosine-containing motif in the cytoplasmic domain. EMBO J. 1993 May;12(5):2219–2228. doi: 10.1002/j.1460-2075.1993.tb05870.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bosshart H., Humphrey J., Deignan E., Davidson J., Drazba J., Yuan L., Oorschot V., Peters P. J., Bonifacino J. S. The cytoplasmic domain mediates localization of furin to the trans-Golgi network en route to the endosomal/lysosomal system. J Cell Biol. 1994 Sep;126(5):1157–1172. doi: 10.1083/jcb.126.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Card J. P., Rinaman L., Lynn R. B., Lee B. H., Meade R. P., Miselis R. R., Enquist L. W. Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis. J Neurosci. 1993 Jun;13(6):2515–2539. doi: 10.1523/JNEUROSCI.13-06-02515.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Darlington R. W., Moss L. H., 3rd Herpesvirus envelopment. J Virol. 1968 Jan;2(1):48–55. doi: 10.1128/jvi.2.1.48-55.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  6. Gershon A. A., Sherman D. L., Zhu Z., Gabel C. A., Ambron R. T., Gershon M. D. Intracellular transport of newly synthesized varicella-zoster virus: final envelopment in the trans-Golgi network. J Virol. 1994 Oct;68(10):6372–6390. doi: 10.1128/jvi.68.10.6372-6390.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grose C. Glycoproteins of varicella-zoster virus and their herpes simplex virus homologs. Rev Infect Dis. 1991 Nov-Dec;13 (Suppl 11):S960–S963. doi: 10.1093/clind/13.supplement_11.s960. [DOI] [PubMed] [Google Scholar]
  8. Grose C., Litwin V. Immunology of the varicella-zoster virus glycoproteins. J Infect Dis. 1988 May;157(5):877–881. doi: 10.1093/infdis/157.5.877. [DOI] [PubMed] [Google Scholar]
  9. Humphrey J. S., Peters P. J., Yuan L. C., Bonifacino J. S. Localization of TGN38 to the trans-Golgi network: involvement of a cytoplasmic tyrosine-containing sequence. J Cell Biol. 1993 Mar;120(5):1123–1135. doi: 10.1083/jcb.120.5.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johnson K. F., Chan W., Kornfeld S. Cation-dependent mannose 6-phosphate receptor contains two internalization signals in its cytoplasmic domain. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10010–10014. doi: 10.1073/pnas.87.24.10010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnson K. F., Kornfeld S. A His-Leu-Leu sequence near the carboxyl terminus of the cytoplasmic domain of the cation-dependent mannose 6-phosphate receptor is necessary for the lysosomal enzyme sorting function. J Biol Chem. 1992 Aug 25;267(24):17110–17115. [PubMed] [Google Scholar]
  12. Kodama H., Abe T., Takama M., Takahashi I., Kodama M., Nishimura M. Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study. J Histochem Cytochem. 1993 Oct;41(10):1529–1535. doi: 10.1177/41.10.8245411. [DOI] [PubMed] [Google Scholar]
  13. Ladinsky M. S., Howell K. E. An electron microscopic study of TGN38/41 dynamics. J Cell Sci Suppl. 1993;17:41–47. doi: 10.1242/jcs.1993.supplement_17.7. [DOI] [PubMed] [Google Scholar]
  14. MORGAN C., ROSE H. M., HOLDEN M., JONES E. P. Electron microscopic observations on the development of herpes simplex virus. J Exp Med. 1959 Oct 1;110:643–656. doi: 10.1084/jem.110.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin S., Reaves B., Banting G., Gould G. W. Analysis of the co-localization of the insulin-responsive glucose transporter (GLUT4) and the trans Golgi network marker TGN38 within 3T3-L1 adipocytes. Biochem J. 1994 Jun 15;300(Pt 3):743–749. doi: 10.1042/bj3000743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matovcik L. M., Goodhouse J., Farquhar M. G. The recycling itinerary of the 46 kDa mannose 6-phosphate receptor--Golgi to late endosomes--coincides with that of the 215 kDa M6PR. Eur J Cell Biol. 1990 Dec;53(2):203–211. [PubMed] [Google Scholar]
  17. Pagano R. E., Sepanski M. A., Martin O. C. Molecular trapping of a fluorescent ceramide analogue at the Golgi apparatus of fixed cells: interaction with endogenous lipids provides a trans-Golgi marker for both light and electron microscopy. J Cell Biol. 1989 Nov;109(5):2067–2079. doi: 10.1083/jcb.109.5.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ponnambalam S., Rabouille C., Luzio J. P., Nilsson T., Warren G. The TGN38 glycoprotein contains two non-overlapping signals that mediate localization to the trans-Golgi network. J Cell Biol. 1994 Apr;125(2):253–268. doi: 10.1083/jcb.125.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reaves B., Banting G. Perturbation of the morphology of the trans-Golgi network following Brefeldin A treatment: redistribution of a TGN-specific integral membrane protein, TGN38. J Cell Biol. 1992 Jan;116(1):85–94. doi: 10.1083/jcb.116.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reaves B., Wilde A., Banting G. Identification, molecular characterization and immunolocalization of an isoform of the trans-Golgi-network (TGN)-specific integral membrane protein TGN38. Biochem J. 1992 Apr 15;283(Pt 2):313–316. doi: 10.1042/bj2830313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schulze-Garg C., Böker C., Nadimpalli S. K., von Figura K., Hille-Rehfeld A. Tail-specific antibodies that block return of 46,000 M(r) mannose 6-phosphate receptor to the trans-Golgi network. J Cell Biol. 1993 Aug;122(3):541–551. doi: 10.1083/jcb.122.3.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schäfer W., Stroh A., Berghöfer S., Seiler J., Vey M., Kruse M. L., Kern H. F., Klenk H. D., Garten W. Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin. EMBO J. 1995 Jun 1;14(11):2424–2435. doi: 10.1002/j.1460-2075.1995.tb07240.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takahashi S., Nakagawa T., Banno T., Watanabe T., Murakami K., Nakayama K. Localization of furin to the trans-Golgi network and recycling from the cell surface involves Ser and Tyr residues within the cytoplasmic domain. J Biol Chem. 1995 Nov 24;270(47):28397–28401. doi: 10.1074/jbc.270.47.28397. [DOI] [PubMed] [Google Scholar]
  24. Tümer Z., Vural B., Tønnesen T., Chelly J., Monaco A. P., Horn N. Characterization of the exon structure of the Menkes disease gene using vectorette PCR. Genomics. 1995 Apr 10;26(3):437–442. doi: 10.1016/0888-7543(95)80160-n. [DOI] [PubMed] [Google Scholar]
  25. Voorhees P., Deignan E., van Donselaar E., Humphrey J., Marks M. S., Peters P. J., Bonifacino J. S. An acidic sequence within the cytoplasmic domain of furin functions as a determinant of trans-Golgi network localization and internalization from the cell surface. EMBO J. 1995 Oct 16;14(20):4961–4975. doi: 10.1002/j.1460-2075.1995.tb00179.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Watanabe H., Grubb J. H., Sly W. S. The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of beta-glucuronidase. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8036–8040. doi: 10.1073/pnas.87.20.8036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Whitney J. A., Gomez M., Sheff D., Kreis T. E., Mellman I. Cytoplasmic coat proteins involved in endosome function. Cell. 1995 Dec 1;83(5):703–713. doi: 10.1016/0092-8674(95)90183-3. [DOI] [PubMed] [Google Scholar]
  28. Wong S. H., Hong W. The SXYQRL sequence in the cytoplasmic domain of TGN38 plays a major role in trans-Golgi network localization. J Biol Chem. 1993 Oct 25;268(30):22853–22862. [PubMed] [Google Scholar]
  29. Zhu Z., Gershon M. D., Hao Y., Ambron R. T., Gabel C. A., Gershon A. A. Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network. J Virol. 1995 Dec;69(12):7951–7959. doi: 10.1128/jvi.69.12.7951-7959.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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