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

D. B. Williams, S. J. Swiedler, Gerald Warren Hart

Research output: Contribution to journalArticlepeer-review

Abstract

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-2K(k) and H-2D(k), at the cell surface were compared and found to be remarkably different. Newly synthesized H-2K(k) is transported rapidly such that all radiolabeled molecules reach the surface within 1 h. In contrast, the H-2D(k) 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-2D(k) 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-2D(k) 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-2D(k) heavy chain to associate with β2-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-2K(k) and H-2D(k) are highly homologous (≥80%) indicates that this process can be strongly influenced by limited alterations in protein structure.

Original languageEnglish (US)
Pages (from-to)725-734
Number of pages10
JournalJournal of Cell Biology
Volume101
Issue number3
StatePublished - 1985

ASJC Scopus subject areas

  • Cell Biology

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