Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1985 Feb 1;100(2):633–637. doi: 10.1083/jcb.100.2.633

Rapid endocytosis of the transferrin receptor in the absence of bound transferrin

PMCID: PMC2113434  PMID: 2857182

Abstract

The rate of endocytosis of transferrin receptors, occupied or unoccupied with transferrin, was measured on the cell line K562. At 37 degrees C, receptors, radioiodinated on the cell surface at 4 degrees C, were internalized equally rapidly in the presence or absence of transferrin. In both cases, 50% of the labeled receptors became resistant to externally added trypsin in 5 min. An antitransferrin antibody was used to show directly that the receptors had entered the cells without bound transferrin. The distribution of the receptors on the cell surface was revealed by antibody and protein A-gold staining after prolonged incubation in the presence or absence of transferrin. The receptors were concentrated in coated pits under both conditions. The data suggest that endocytosis of transferrin receptors is not "triggered" by ligand binding and raise the possibility that ligand- induced down-regulation of surface receptors may not occur by this mechanism. Instead receptors may be recognized as being ligand- occupied, not at the cell surface, but at some other site in the recycling pathway such as the endosome.

Full Text

The Full Text of this article is available as a PDF (636.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson R. G., Brown M. S., Beisiegel U., Goldstein J. L. Surface distribution and recycling of the low density lipoprotein receptor as visualized with antireceptor antibodies. J Cell Biol. 1982 Jun;93(3):523–531. doi: 10.1083/jcb.93.3.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Basu S. K., Goldstein J. L., Anderson R. G., Brown M. S. Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts. Cell. 1981 May;24(2):493–502. doi: 10.1016/0092-8674(81)90340-8. [DOI] [PubMed] [Google Scholar]
  3. Berg T., Blomhoff R., Naess L., Tolleshaug H., Drevon C. A. Monensin inhibits receptor-mediated endocytosis of asialoglycoproteins in rat hepatocytes. Exp Cell Res. 1983 Oct 15;148(2):319–330. doi: 10.1016/0014-4827(83)90156-8. [DOI] [PubMed] [Google Scholar]
  4. Bleil J. D., Bretscher M. S. Transferrin receptor and its recycling in HeLa cells. EMBO J. 1982;1(3):351–355. doi: 10.1002/j.1460-2075.1982.tb01173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown M. S., Anderson R. G., Goldstein J. L. Recycling receptors: the round-trip itinerary of migrant membrane proteins. Cell. 1983 Mar;32(3):663–667. doi: 10.1016/0092-8674(83)90052-1. [DOI] [PubMed] [Google Scholar]
  6. Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ciechanover A., Schwartz A. L., Lodish H. F. The asialoglycoprotein receptor internalizes and recycles independently of the transferrin and insulin receptors. Cell. 1983 Jan;32(1):267–275. doi: 10.1016/0092-8674(83)90517-2. [DOI] [PubMed] [Google Scholar]
  8. Dautry-Varsat A., Ciechanover A., Lodish H. F. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2258–2262. doi: 10.1073/pnas.80.8.2258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dunn W. A., Hubbard A. L. Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics. J Cell Biol. 1984 Jun;98(6):2148–2159. doi: 10.1083/jcb.98.6.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ekblom P., Thesleff I., Lehto V. P., Virtanen I. Distribution of the transferrin receptor in normal human fibroblasts and fibrosarcoma cells. Int J Cancer. 1983 Jan 15;31(1):111–117. doi: 10.1002/ijc.2910310118. [DOI] [PubMed] [Google Scholar]
  11. Gavin J. R., 3rd, Roth J., Neville D. M., Jr, de Meyts P., Buell D. N. Insulin-dependent regulation of insulin receptor concentrations: a direct demonstration in cell culture. Proc Natl Acad Sci U S A. 1974 Jan;71(1):84–88. doi: 10.1073/pnas.71.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldstein J. L., Anderson R. G., Brown M. S. Coated pits, coated vesicles, and receptor-mediated endocytosis. Nature. 1979 Jun 21;279(5715):679–685. doi: 10.1038/279679a0. [DOI] [PubMed] [Google Scholar]
  13. Gorden P., Carpentier J. L., Cohen S., Orci L. Epidermal growth factor: morphological demonstration of binding, internalization, and lysosomal association in human fibroblasts. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5025–5029. doi: 10.1073/pnas.75.10.5025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hubbard A. L., Cohn Z. A. Externally disposed plasma membrane proteins. I. Enzymatic iodination of mouse L cells. J Cell Biol. 1975 Feb;64(2):438–460. doi: 10.1083/jcb.64.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King A. C., Hernaez-Davis L., Cuatrecasas P. Lysomotropic amines cause intracellular accumulation of receptors for epidermal growth factor. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3283–3287. doi: 10.1073/pnas.77.6.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klausner R. D., Ashwell G., van Renswoude J., Harford J. B., Bridges K. R. Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2263–2266. doi: 10.1073/pnas.80.8.2263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klausner R. D., Harford J., van Renswoude J. Rapid internalization of the transferrin receptor in K562 cells is triggered by ligand binding or treatment with a phorbol ester. Proc Natl Acad Sci U S A. 1984 May;81(10):3005–3009. doi: 10.1073/pnas.81.10.3005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Krupp M., Lane M. D. On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell. J Biol Chem. 1981 Feb 25;256(4):1689–1694. [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Mellman I., Plutner H., Ukkonen P. Internalization and rapid recycling of macrophage Fc receptors tagged with monovalent antireceptor antibody: possible role of a prelysosomal compartment. J Cell Biol. 1984 Apr;98(4):1163–1169. doi: 10.1083/jcb.98.4.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Townsend R. R., Wall D. A., Hubbard A. L., Lee Y. C. Rapid release of galactose-terminated ligands after endocytosis by hepatic parenchymal cells: evidence for a role of carbohydrate structure in the release of internalized ligand from receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(2):466–470. doi: 10.1073/pnas.81.2.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Van Leuven F., Cassiman J. J., Van Den Berghe H. Primary amines inhibit recycling of alpha 2M receptors in fibroblasts. Cell. 1980 May;20(1):37–43. doi: 10.1016/0092-8674(80)90232-9. [DOI] [PubMed] [Google Scholar]
  23. Wall D. A., Hubbard A. L. Galactose-specific recognition system of mammalian liver: receptor distribution on the hepatocyte cell surface. J Cell Biol. 1981 Sep;90(3):687–696. doi: 10.1083/jcb.90.3.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Watts C. In situ 125I-labelling of endosome proteins with lactoperoxidase conjugates. EMBO J. 1984 Sep;3(9):1965–1970. doi: 10.1002/j.1460-2075.1984.tb02077.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES