Home LiteratureArticle Details
PMID: 3972890 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutations in the cytoplasmic domain of the influenza virus hemagglutinin affect different stages of intracellular transport.

The Journal of cell biology ·Vol. 100 ·No. 3 ·1985-03-00 ·Pages 704-14

Doyle C, Roth MG, Sambrook J, Gething MJ

Abstract

Mutations have been introduced into the cloned DNA sequences coding for influenza virus hemagglutinin (HA), and the resulting mutant genes have been expressed in simian cells by the use of SV40-HA recombinant viral vectors. In this study we analyzed the effect of specific alterations in the cytoplasmic domain of the HA molecule on its rate of biosynthesis and transport, cellular localization, and biological activity. Several of the mutants displayed abnormalities in the pathway of transport from the endoplasmic reticulum to the cell surface. One mutant HA remained within the endoplasmic reticulum; others were delayed in reaching the Golgi apparatus after core glycosylation had been completed in the endoplasmic reticulum, but then progressed at a normal rate from the Golgi apparatus to the cell surface; another was delayed in transport from the Golgi apparatus to the plasma membrane. However, two mutants were indistinguishable from wild-type HA in their rate of movement from the endoplasmic reticulum through the Golgi apparatus to the cell surface. We conclude that changes in the cytoplasmic domain can powerfully influence the rate of intracellular transport and the efficiency with which HA reaches the cell surface. Nevertheless, absolute conservation of this region of the molecule is not required for maturation and efficient expression of a biologically active HA on the surface of infected cells.

MeSH Terms
Animals Biological Transport, Active Cell Membrane/immunology Cells, Cultured Cloning, Molecular Cytoplasm/immunology Endoplasmic Reticulum/immunology Golgi Apparatus/immunology Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral/genetics Mutation
Chemicals
Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinins, Viral
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Doyle C
Roth M G
Sambrook J
Gething M J
References (55)
55 references, click to expand
  1. Mechanisms for the incorporation of proteins in membranes and organelles.
    J Cell Biol. 1982 Jan;92(1):1-22 PMID: 7035466
  2. Mutations of the Rous sarcoma virus env gene that affect the transport and subcellular location of the glycoprotein products.
    J Cell Biol. 1984 Dec;99(6):2011-23 PMID: 6094591
  3. Enchancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethylaminoethyl-dextran.
    J Natl Cancer Inst. 1968 Aug;41(2):351-7 PMID: 4299537
  4. Influenza virus structural and nonstructural proteins in infected cells and their plasma membranes.
    Virology. 1971 Dec;46(3):830-43 PMID: 5167660
  5. Purification and properties of an endo-beta-N-acetylglucosaminidase from Streptomyces griseus.
    J Biol Chem. 1974 Feb 10;249(3):811-7 PMID: 4204552
  6. Studies on the primary structure of the influenza virus hemagglutinin.
    Proc Natl Acad Sci U S A. 1975 Jan;72(1):93-7 PMID: 1054518
  7. Intracellular aspects of the process of protein synthesis.
    Science. 1975 Aug 1;189(4200):347-58 PMID: 1096303
  8. Tunicamycin inhibition of polyisoprenyl N-acetylglucosaminyl pyrophosphate formation in calf-liver microsomes.
    Biochem Biophys Res Commun. 1975 Jul 8;65(1):248-57 PMID: 167767
  9. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  10. Antibody-induced linkages of plasma membrane proteins to intracellular actomyosin-containing filaments in cultured fibroblasts.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5584-8 PMID: 146200
  11. The synthesis of complex-type oligosaccharides. II. Characterization of the processing intermediates in the synthesis of the complex oligosaccharide units of the vesicular stomatitis virus G protein.
    J Biol Chem. 1978 Nov 10;253(21):7771-8 PMID: 212435
  12. Evidence for covalent attachment of fatty acids to Sindbis virus glycoproteins.
    Proc Natl Acad Sci U S A. 1979 Apr;76(4):1687-91 PMID: 287008
  13. The mechanism of protein secretion across membranes.
    Nature. 1980 Jan 31;283(5746):433-8 PMID: 7352023
  14. Translocation of proteins across membranes: the signal hypothesis and beyond.
    Symp Soc Exp Biol. 1979;33:9-36 PMID: 524275
  15. Intracellular protein topogenesis.
    Proc Natl Acad Sci U S A. 1980 Mar;77(3):1496-500 PMID: 6929499
  16. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain.
    Cell. 1980 Jun;20(2):303-12 PMID: 6771019
  17. Cloning and DNA sequence of double-stranded copies of haemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in human influenza virus.
    Nature. 1980 Sep 25;287(5780):301-6 PMID: 7421990
  18. Deletion mutants of SV40 that affect the structure of viral tumor antigens.
    Cold Spring Harb Symp Quant Biol. 1980;44 Pt 1,:285-91 PMID: 6253142
  19. Biosynthesis of HLA-A and HLA-B antigens in vivo.
    J Biol Chem. 1980 Oct 25;255(20):9678-84 PMID: 7000762
  20. Intracellular transport of secretory and membrane proteins in hepatoma cells infected by vesicular stomatitis virus.
    Cell. 1980 Dec;22(3):709-17 PMID: 6257395
  21. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.
    Nature. 1981 Jan 29;289(5796):366-73 PMID: 7464906
  22. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation.
    Nature. 1981 Jan 29;289(5796):373-8 PMID: 6162101
  23. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing.
    J Mol Biol. 1980 Oct 25;143(2):161-78 PMID: 6260957
  24. Major histocompatibility antigens: the human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules.
    Cell. 1981 May;24(2):287-99 PMID: 7016338
  25. Synthesis and processing of asparagine-linked oligosaccharides.
    Annu Rev Biochem. 1981;50:555-83 PMID: 7023366
  26. Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances.
    J Cell Biol. 1981 Sep;90(3):656-64 PMID: 7287819
  27. Cell-surface expression of influenza haemagglutinin from a cloned DNA copy of the RNA gene.
    Nature. 1981 Oct 22;293(5834):620-5 PMID: 6270568
  28. Antibodies to the Golgi complex and the rough endoplasmic reticulum.
    J Cell Biol. 1982 Jan;92(1):92-107 PMID: 7199056
  29. Passage of viral membrane proteins through the Golgi complex.
    J Mol Biol. 1981 Nov 15;152(4):663-98 PMID: 7038131
  30. Two distinct intracellular pathways transport secretory and membrane glycoproteins to the surface of pituitary tumor cells.
    Cell. 1982 Jan;28(1):51-9 PMID: 6279313
  31. The phosphomannosyl recognition system for intracellular and intercellular transport of lysosomal enzymes.
    J Cell Biochem. 1982;18(1):67-85 PMID: 6279685
  32. Evidence for a glycoprotein "signal" involved in transport between subcellular organelles. Two membrane glycoproteins encoded by murine leukemia virus reach the cell surface at different rates.
    J Biol Chem. 1982 Dec 10;257(23):14011-7 PMID: 7142193
  33. Construction of influenza haemagglutinin genes that code for intracellular and secreted forms of the protein.
    Nature. 1982 Dec 16;300(5893):598-603 PMID: 7144911
  34. Kinetics of serum protein secretion by cultured hepatoma cells. Evidence for multiple secretory pathways.
    J Biol Chem. 1983 Mar 10;258(5):3304-8 PMID: 6186665
  35. High efficiency polyoma DNA transfection of chloroquine treated cells.
    Nucleic Acids Res. 1983 Mar 11;11(5):1295-308 PMID: 6298741
  36. Nucleotide sequence of Rous sarcoma virus.
    Cell. 1983 Mar;32(3):853-69 PMID: 6299578
  37. Analysis of the hemagglutinin glycoprotein from mutants of vaccinia virus that accumulates on the nuclear envelope.
    Cell. 1983 Jun;33(2):423-34 PMID: 6861204
  38. Studies on transformation of Escherichia coli with plasmids.
    J Mol Biol. 1983 Jun 5;166(4):557-80 PMID: 6345791
  39. Hepatoma secretory proteins migrate from rough endoplasmic reticulum to Golgi at characteristic rates.
    Nature. 1983 Jul 7-13;304(5921):80-3 PMID: 6866094
  40. A genetic system for analysis of staphylococcal nuclease.
    Gene. 1983 May-Jun;22(2-3):181-9 PMID: 6307819
  41. Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation.
    Cell. 1983 Aug;34(1):233-43 PMID: 6883510
  42. Expression of Semliki Forest virus proteins from cloned complementary DNA. II. The membrane-spanning glycoprotein E2 is transported to the cell surface without its normal cytoplasmic domain.
    J Cell Biol. 1983 Sep;97(3):652-8 PMID: 6688424
  43. Altered cytoplasmic domains affect intracellular transport of the vesicular stomatitis virus glycoprotein.
    Cell. 1983 Sep;34(2):513-24 PMID: 6352053
  44. Expression and function of transplantation antigens with altered or deleted cytoplasmic domains.
    Cell. 1983 Sep;34(2):535-44 PMID: 6604582
  45. Mechanisms of protein localization.
    Microbiol Rev. 1983 Sep;47(3):313-44 PMID: 6355805
  46. Intracellular vesicles involved in the transport of Semliki Forest virus membrane proteins to the cell surface.
    EMBO J. 1983;2(11):2001-6 PMID: 6641709
  47. Vesicular stomatitis virus glycoprotein, albumin, and transferrin are transported to the cell surface via the same Golgi vesicles.
    J Cell Biol. 1983 Dec;97(6):1815-22 PMID: 6315744
  48. The mannose-6-phosphate receptor for lysosomal enzymes is concentrated in cis Golgi cisternae.
    Cell. 1984 Feb;36(2):295-307 PMID: 6319015
  49. Construction, expression and recognition of an H-2 molecule lacking its carboxyl terminus.
    Nature. 1984 Feb 2-8;307(5950):432-6 PMID: 6363940
  50. Four secretory proteins synthesized by hepatocytes are transported from endoplasmic reticulum to Golgi complex at different rates.
    EMBO J. 1984 Jan;3(1):147-52 PMID: 6538481
  51. Viral glycoproteins destined for apical or basolateral plasma membrane domains traverse the same Golgi apparatus during their intracellular transport in doubly infected Madin-Darby canine kidney cells.
    J Cell Biol. 1984 Apr;98(4):1304-19 PMID: 6325468
  52. Fatty acid-acylated proteins in secretory mutants of Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Apr;4(4):688-94 PMID: 6371494
  53. Density of newly synthesized plasma membrane proteins in intracellular membranes II. Biochemical studies.
    J Cell Biol. 1984 Jun;98(6):2142-7 PMID: 6563038
  54. Pre- and post-Golgi vacuoles operate in the transport of Semliki Forest virus membrane glycoproteins to the cell surface.
    Cell. 1984 Sep;38(2):535-49 PMID: 6432345
  55. Selective extraction of polyoma DNA from infected mouse cell cultures.
    J Mol Biol. 1967 Jun 14;26(2):365-9 PMID: 4291934
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.100.3.704
Published
1985-03-00
Pages
704-14
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2113518
Subset
IM
Grants
NIAID NIH HHS · AI19630 · United States
External Links
PubMed source DOI: 10.1083/jcb.100.3.704 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2