The Journal of Cell Biology, Vol 101, 725-734, Copyright © 1985 by The Rockefeller University Press

ARTICLES

Intracellular transport of membrane glycoproteins: two closely related histocompatibility antigens differ in their rates of transit to the cell surface

DB Williams, SJ Swiedler and GW Hart

The intracellular transport of two closely related membrane glycoproteins was studied in the murine B cell lymphoma line, AKTB-1b. Using pulse-chase radiolabeling, the kinetics of appearance of the class I histocompatibility antigens, H-2Kk and H-2Dk, at the cell surface were compared and found to be remarkably different. Newly synthesized H-2Kk is transported rapidly such that all radiolabeled molecules reach the surface within 1 h. In contrast, the H-2Dk antigen is transported slowly with a half-time of 4-5 h. The rates of surface appearance for the two antigens closely resemble the rates at which their Asn-linked oligosaccharides mature from endoglucosaminidase H (endo H)-sensitive to endo H-resistant forms, a process that occurs in the Golgi apparatus. This suggests that the rate-limiting step in the transport of H-2Dk to the cell surface occurs before the formation of endo H-resistant oligosaccharides in the Golgi apparatus. Subcellular fractionation experiments confirmed this conclusion by identifying the endoplasmic reticulum (ER) as the site where the H-2Dk antigen accumulates. The retention of this glycoprotein in the ER does not appear to be due to a lack of solubility or an inability of the H-2Dk heavy chain to associate with beta 2-microglobulin. Our data is inconsistent with a passive membrane flow mechanism for the intracellular transport of membrane glycoproteins. Rather, it suggests that one or more receptors localized to the ER membrane may mediate the selective transport of membrane glycoproteins out of the ER to the Golgi apparatus. The fact that H-2Kk and H-2Dk are highly homologous (greater than or equal to 80%) indicates that this process can be strongly influenced by limited alterations in protein structure.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Garstka, M., Borchert, B., Al-Balushi, M., Praveen, P., Kuhl, N., Majoul, I., Duden, R., Springer, S. (2007). Peptide-receptive Major Histocompatibility Complex Class I Molecules Cycle between Endoplasmic Reticulum and cis-Golgi in Wild-type Lymphocytes. J. Biol. Chem. 282: 30680-30690 [Abstract] [Full Text]  
• Ploegh, H. L. (2007). The Peptide Cargo of Class I Molecules: Not Just Passive Passengers. J. Immunol. 179: 4299-4300 [Full Text]  
• Moffat, K., Knox, C., Howell, G., Clark, S. J., Yang, H., Belsham, G. J., Ryan, M., Wileman, T. (2007). Inhibition of the Secretory Pathway by Foot-and-Mouth Disease Virus 2BC Protein Is Reproduced by Coexpression of 2B with 2C, and the Site of Inhibition Is Determined by the Subcellular Location of 2C. J. Virol. 81: 1129-1139 [Abstract] [Full Text]  
• Tourdot, S., Nejmeddine, M., Powis, S. J., Gould, K. G. (2005). Different MHC Class I Heavy Chains Compete with Each Other for Folding Independently of {beta}2-Microglobulin and Peptide. J. Immunol. 174: 925-933 [Abstract] [Full Text]  
• Mueller, S. N., Jones, C. M., Chen, W., Kawaoka, Y., Castrucci, M. R., Heath, W. R., Carbone, F. R. (2003). The Early Expression of Glycoprotein B from Herpes Simplex Virus Can Be Detected by Antigen-Specific CD8+ T Cells. J. Virol. 77: 2445-2451 [Abstract] [Full Text]  
• Baldwin, T. A., Ostergaard, H. L. (2002). The Protein-tyrosine Phosphatase CD45 Reaches the Cell Surface via Golgi-dependent and -independent Pathways. J. Biol. Chem. 277: 50333-50340 [Abstract] [Full Text]  
• Tourdot, S., Gould, K. G. (2002). Competition Between MHC Class I Alleles for Cell Surface Expression Alters CTL Responses to Influenza A Virus. J. Immunol. 169: 5615-5621 [Abstract] [Full Text]  
• Yu, Y. Y. L., Harris, M. R., Lybarger, L., Kimpler, L. A., Myers, N. B., Virgin IV, H. W., Hansen, T. H. (2002). Physical Association of the K3 Protein of Gamma-2 Herpesvirus 68 with Major Histocompatibility Complex Class I Molecules with Impaired Peptide and {beta}2-Microglobulin Assembly. J. Virol. 76: 2796-2803 [Abstract] [Full Text]  
• Qian, S.-B., Chen, S.-S. (2000). Blocked transport of soluble Kb molecules containing connecting peptide segment involved in calnexin association. Int Immunol 12: 1409-1416 [Abstract] [Full Text]  
• Dela Cruz, C. S., Tan, R., Rowland-Jones, S. L., Barber, B. H. (2000). Creating HIV-1 reverse transcriptase cytotoxic T lymphocyte target structures by HLA-A2 heavy chain modifications. Int Immunol 12: 1293-1302 [Abstract] [Full Text]  
• Baumann, N. A., Vidugiriene, J., Machamer, C. E., Menon, A. K. (2000). Cell Surface Display and Intracellular Trafficking of Free Glycosylphosphatidylinositols in Mammalian Cells. J. Biol. Chem. 275: 7378-7389 [Abstract] [Full Text]  
• Anton, L. C., Snyder, H. L., Bennink, J. R., Vinitsky, A., Orlowski, M., Porgador, A., Yewdell, J. W. (1998). Dissociation of Proteasomal Degradation of Biosynthesized Viral Proteins from Generation of MHC Class I-Associated Antigenic Peptides. J. Immunol. 160: 4859-4868 [Abstract] [Full Text]  
• Cox, J., Yewdell, J., Eisenlohr, L., Johnson, P., Bennink, J. (1990). Antigen presentation requires transport of MHC class I molecules from the endoplasmic reticulum. Science 247: 715-718 [Abstract]  
• Yewdell, J., Bennink, J. (1989). Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science 244: 1072-1075 [Abstract]  
• Carbone, F.R., Hosken, N.A., Moore, M.W., Bevan, M.J. (1989). Class I MHC-restricted Cytotoxic Responses to Soluble Protein Antigen. Cold Spring Harb Symp Quant Biol 54: 551-555 [Abstract]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents