Internalization of Hormone Receptor Complexes: Route and Significance

  • Barry I. Posner
  • Masood N. Khan
  • Denis G. Kay
  • John J. M. Bergeron
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 205)


Receptor-mediated endocytosis is a general process by which a wide variety of ligands are taken up with high specificity and affinity into cells. In this review we shall primarily discuss data in regard to the internalization of peptide hormones, especially insulin, but it is noteworthy that there are similarities as well as interesting differences by which membrane-bound lectins, immune complexes, viruses, toxins, etc. are handled by cells (Bergeron et al., 1985).


Insulin Receptor Peptide Hormone Asialoglycoprotein Receptor Golgi Element Endosomal System 
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  1. Attie, A. D., Pittman, R. C., and Steinberg, D., 1982, Hepatic catabolism of low density lipoprotein: Mechanisms and metabolic consequences, Hepatology, 2: 269–281.PubMedCrossRefGoogle Scholar
  2. Basu, S. K., Goldstein, J. K., Anderson, R. G. W., and Brown, M. S., 1981, Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts, Cell, 24: 493–502.PubMedCrossRefGoogle Scholar
  3. Bergeron, J. J. M., Ehrenreich, J. H., Siekevitz, P., and Palade, G. E., 1973, Golgi fractions prepared from rat liver homogenates: Isolation procedure and morphological characterization, J. Cell Biol., 59: 73–88.PubMedCrossRefGoogle Scholar
  4. Bergeron, J. J. M., Sikstrom, R., Hand, A. R., and Posner, B. I., 1979, Binding and uptake of 125I-insulin into rat liver hepatocytes and endothelium, J. Cell. Biol., 80: 427–443.PubMedCrossRefGoogle Scholar
  5. Bergeron, J. J. M., Resch, L., Rachubinski, R., Patel, B., and Posner, B. I., 1983, Effect of colchicine on internalization of prolactin in female rat liver: An in vivo radioautographic study, J. Cell Biol., 96: 875–886.PubMedCrossRefGoogle Scholar
  6. Bergeron, J. J. M., Cruz, J., Khan, M. N., and Posner, B. I., 1985, Uptake of insulin and other ligands into receptor-rich endocytic components of target cells: The endosomal apparatus, Ann. Rev. Physiol., 47: 383–403.CrossRefGoogle Scholar
  7. Berhanu, P., Olefsky, J. M., Tsai, F., Thamm, P., Saunders, D., and Brandenburg, D., 1982, Internalization and molecular processing of insulin receptors in isolated rat adipocytes, Proc. Natl. Acad. Sci. USA, 79: 4069–4073.PubMedCrossRefGoogle Scholar
  8. Catt, K. J., Harwood, J. P., Aquilera, G., and Dufau, M. L., 1979, Hormonal regulation of peptide receptors and target cell responses, Nature, 280: 109.PubMedCrossRefGoogle Scholar
  9. Chao, Y. S., Jones, A. L., Hradek, G. I., Windler, E. E. T., and Havel, R. J., 1981, Autoradiographic localization of low density lipoproteins in the liver of normal and estrogen-treated rats, Proc. Natl. Acad. Sci. USA, 78: 597–601.PubMedCrossRefGoogle Scholar
  10. Cohen, S., and Fava, R. A., 1985, Internalization of functional epidermal growth factor: Receptor kinase complexes in A-431 cells, J. Biol. Chem., 260: 12351–12358.PubMedGoogle Scholar
  11. Courtoy, P. J., Quintart, J., and Baudhuin, F., 1984, Shift of equilibrium density induced by 3, 3-diaminobenzidine cytochemistry: A new procedure for the analysis and purification of peroxidasecontaining organelles, J. Cell Biol., 98: 870–876.PubMedCrossRefGoogle Scholar
  12. Cruz, J., Posner, B. I., and Bergeron, J. J. M., 1984, Receptor-mediated endocytosis of 1251-insulin into pancreatic acinar cells in vivo, Endocrinology, 115: 1996–2008.PubMedCrossRefGoogle Scholar
  13. Duve, C., de Bousy, T., Poole, B., Trouet, A., Tulkens, P., and Van Hoof, F., 1974, Lysosomotropic agents, Biochem. Pharmacol., 23: 2495–2531.PubMedCrossRefGoogle Scholar
  14. Desbuquois, B., Lopez, S., and Burlet, H., 1982, Ligand-induced translocation of insulin receptors in intact rat liver, J. Biol. Chem., 257: 10852–10860.PubMedGoogle Scholar
  15. Dickson, R. B., Willingham, M. C., and Pastan, I., 1981, 2-macroglobulin absorbed to colloidal gold: A new probe in the study of receptor-mediated endocytosis, J. Cell Biol., 89: 29–34.Google Scholar
  16. Dunn, W. A., Hubbard, A. L., and Aronson, A. L., 1980, Low temperature selectively inhibits fusion between pinocytic vesicles and lysosomes during heterophagy of 125I-asialofetuin by the perfused rat liver, J. Biol. Chem., 255: 5971–5978.PubMedGoogle Scholar
  17. Ehrenreich, J. H., Bergeron, J. J. M., Siekevitz, P., and Palade, G. E., 1973, Golgi fractions prepared from rat liver homogenates: Isolation procedure and morphological characterization, J. Cell Biol., 59: 45–72.PubMedCrossRefGoogle Scholar
  18. Enns, C. A., Larrick J. W., Suomalainen, H., Schroder, J., and Sussman, H. H., 1983, Co-migration and internalization of transferrin and its receptor on K562 cells, J. Cell Biol., 97: 579–585.PubMedCrossRefGoogle Scholar
  19. Fehlmann, M., Carpentier, J.-L., Le Cam, A., Thamm, P., Saunders, D., Brandenburg, D., Orci, L., and Freychet, P., 1982, Biochemical and morphological evidence that the insulin receptor is internalized with insulin in hepatocytes, J. Cell Biol., 93: 82–87.PubMedCrossRefGoogle Scholar
  20. Fehlmann, M., Carpentier, J.-L., Van Obberghen, E., Freychet, P., Thamm, P., Saunders, D., Brandenburg, D., and Orci, L., 1982a, Internalized insulin receptors are recycled to the cell surface in rat hepatocytes, Proc. Natl. Acad. Sci. USA, 79: 5921–5925.PubMedCrossRefGoogle Scholar
  21. Galloway, C. J., Dean, C. E., Marsh, M., Rudnick, G., and Mellman, I., 1983, Acidification of macrophage and fibroblast endocytic vesicles in vitro, Proc. Natl. Acad. Sci. USA, 80: 3334–3339.PubMedCrossRefGoogle Scholar
  22. Gavin, J. R. III, Roth, J., Neville, D. M. Jr., De Meyts, F., and Buell, D. N., 1974, Insulin-dependent regulation of insulin receptor concentrations: A direct demonstration in cell culture, Proc. Natl. Acad. Sci. USA, 71: 84–88.PubMedCrossRefGoogle Scholar
  23. Geuze, H. J., Slot, J. W., Strous, G. J., Lodish, H. F., and Schwartz, A. A. L., 1983, Intracellular site of asialoglycoprotein receptor-ligand uncoupling: Double-label immunoelectron microscopy during receptor-mediated endocytosis, Cell, 32: 277–287.PubMedCrossRefGoogle Scholar
  24. Geuze, H. J.. Slot. J. W.. and Schwartz, A. L., 1984, Intracellular receptor sorting during endocytosis: Comparative immunoelectron microscopy of multiple receptors in rat liver, Cell, 37: 195–204.PubMedCrossRefGoogle Scholar
  25. Goldstein, J. L., Brown, M. S., Anderson, R. G. W., Russell, D. W., and Schneider, W. J., 1985, Receptor-mediated endocytosis: Concepts emerging from the LDL receptor system, Ann. Rev. Cell Biol., 1: 1–39.PubMedCrossRefGoogle Scholar
  26. Gorden, P., Carpentier, J.-L., Freychett, P., and Orci, L., 1980, Internalization of polypeptide hormones: Mechanism, intracellular localization and significance, Diabetologia, 18: 263–274.PubMedCrossRefGoogle Scholar
  27. Green, A., and Olefsky, J. M., 1982, Evidence for insulin-induced internalization and degradation of insulin receptors in rat adipocytes, Proc. Natl. Acad. Sci. USA, 79: 427–431.PubMedCrossRefGoogle Scholar
  28. Helenius, A., Mellman, J. I., Wall, D., and Hubbard, A., 1983, Endosomes, Trends Biochem. Sci., 7:245–250Google Scholar
  29. Hopkins, C. R., 1983, Intracellular routing of transferrin and transferring receptors in epidermoid carcinoma A431 cells, Cell, 32: 321–330.CrossRefGoogle Scholar
  30. Hunter, I., and Cooper, J. A., 1985, Protein-tyrosine kinases, Ann. Rev. Biochem., 54: 897–930.PubMedCrossRefGoogle Scholar
  31. Jacobs, S., 1985, Immunochemical characterization of receptors for insulin and insulin-like growth factor-1, in: “Molecular Basis of Insulin Action”, M. P. Czech, ed., Plenum Press, New York, pp. 31–43.CrossRefGoogle Scholar
  32. Kay, D. G., Khan, M. N., Posner, B. I., and Bergeron, J. J. M., 1984, 125I-insulin in hepatic Golgi fractions: Application of the diaminobenzidine (DAB)-shift protocol, Biochem. Biophys. Res. Commun., 123: 1144–1148.Google Scholar
  33. Kay, D. G., Lai, W. H., Uchihashi, M., Posner, B. I., and Bergeron, J. J. M., 1985, In vivo internalization of active EGF receptor kinase into rat liver endosomes, J. Cell. Biol., 101:298a (abstr. 1124 ).Google Scholar
  34. Khan, M. N., Posner, B. I., Verma, A. K., Khan, R. J., and Bergeron, J. J. M., 1981, Intracellular hormone receptors: Evidence for insulin and lactogen receptors in a unique vesicle sedimenting in lysosome fractions of rat liver, Proc. Natl. Acad. Sci. USA, 78: 4980–4984.PubMedCrossRefGoogle Scholar
  35. Khan, M. N., Posner, B. I., Khan, R. J., and Bergeron, J. J. M., 1982, Internalization of insulin into rat liver Golgi elements: Evidence for vesicle heterogeneity and the path of intracellular processing, J. Biol. Chem., 257: 5969–5976.PubMedGoogle Scholar
  36. Khan, M. N., Bergeron, J. J. M., and Posner, B. I., 1985, In vivo activation of the insulin receptor protein kinase in rat liver, J. Cell. Biol., 101: 50a (abstr. 185).Google Scholar
  37. Khan, R. J., Khan, M. N., Bergeron, J. J. M. and Posner, B. I., 1985a, Prolactin internalization into rat liver Golgi fractions: Differential effects of chloroquine, Biochim. Biophys. Acta, 838: 77–83.PubMedCrossRefGoogle Scholar
  38. Khan, M. N., Savoie, S., Bergeron, J. J. M., and Posner, B. I., 1985b, Insulin and insulin receptor uptake into Golgi fractions: Effect and possible site of chloroquine action, Diabetes, 34: 1025–1030.PubMedCrossRefGoogle Scholar
  39. Kikuchi, K., Larner, J., Freer, R. J., and Day, A. R., 1981, Effect of insulin fragments on biological activity of insulin and desoctapeptide insulin, I. Potentiation of biological activities, J. Biol. Chem., 256: 9441–9444.PubMedGoogle Scholar
  40. Krupp, M., and Lane, M. D., 1981, On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell, J. Biol. Chem., 256: 1689–1694.PubMedGoogle Scholar
  41. Kuhn, L. C., and Kraehenbuhl, J. P., 1982, The sacrificial receptor-translocation of polymeric IgA across epithelia, Trends Biochem. Sci., 7: 299–302.Google Scholar
  42. Larner, J., Galasko, G., Cheng, K., Depaoli-Roach, A. A., Huang, L., Daggy, P., and Kellogg, J., 1979, Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation, Science, 206; 1408–1410.PubMedCrossRefGoogle Scholar
  43. Marsh, M., and Helenius, A., 1980, Adsorptive endocytosis of Semliki Forest Virus, J. Mol. Biol., 142: 439–454.PubMedCrossRefGoogle Scholar
  44. McKanna, J. A., Haigler, H. T., and Cohen, S., 1979, Hormone receptor topology and dynamics: Morphological analysis using ferritinlabeled epidermal growth factor, Proc. Natl. Acad. Sci. USA, 76: 5689–5693.PubMedCrossRefGoogle Scholar
  45. Mellman, I. S., Plutner, H., Steinman, R. M., Unkeless, J. C., and Cohn, Z. A., 1983, Internalization and degradation of macrophage Fc receptors during receptor-mediated phagocytosis, J. Cell Biol., 96: 887–895.PubMedCrossRefGoogle Scholar
  46. Mock, E. J., and Niswender, G. D., 1983, Differences in the rate of internalization of 1251-labeled human chorionic gonadotropin, luteinizing hormone and epidermal growth factor in ovine luteal cells, Endocrinology, 113: 259.PubMedCrossRefGoogle Scholar
  47. Pastan, I. H., and Willingham, M. C., 1981, Receptor-mediated endocytosis of hormones in cultured cells, Ann. Rev. Physiol., 43: 239–250.CrossRefGoogle Scholar
  48. Pezzino, V., Vigneri, R., Piliam, N. B., and Goldfine, I. D., 1980, Rapid regulation of plasma membrane insulin receptors, Diabetologia, 19: 211–215.PubMedCrossRefGoogle Scholar
  49. Posner, B. I., Kelly. P. A., and Friesen, H. G., 1975, Prolactin receptors in rat liver: Possible induction by prolactin, Science, 187: 57–59.CrossRefGoogle Scholar
  50. Posner, B. I., Josefsberg, Z., and Bergeron, J. J. M., 1979, Intracellular polypeptide hormone receptors: Characterization and induction of prolactin receptors in the Golgi apparatus of rat liver, J. Biol. Chem., 254: 12494–12499.PubMedGoogle Scholar
  51. Posner, B. I., Patel, B., Verma, A. K., and Bergeron, J. J. M., 1980, Uptake of insulin by plasmalemma and Golgi subcellular fractions of rat liver, J. Biol. Chem., 255: 735–741.PubMedGoogle Scholar
  52. Posner, B. I., Bergeron, J. J. M., Josefsberg, Z., Khan, M. N., Khan, R. J., Patel, B. A., Sikstrom, R. A., and Verma, A. K., 1981, Polypeptide hormones: Intracellular receptors and internalization, Rec. Prog. Horm. Res., 37: 539–582.PubMedGoogle Scholar
  53. Posner, B. I., Khan, M. N., and Bergeron, J. J. M., 1982, Endocytosis of peptide hormones and other ligands, Endocrine Rev., 3: 280–298.CrossRefGoogle Scholar
  54. Posner, B. I., Patel, B., Khan., M. N., Bergeron, J. J. M., 1982a, Effect of chloroquine on the internalization of 125I-insulin into subcellular fractions of rat liver: Evidence for an effect of chloroquine on Golgi elements, J. Biol. Chem., 257: 5789–5799.PubMedGoogle Scholar
  55. Posner B. I., Verma, A. K., Patel, B., and Bergeron, J. J. M., 1982b, Effect of colchicine on the uptake of prolactin and insulin into Golgi fractions of rat liver, J. Cell. Biol., 93: 560–567.PubMedCrossRefGoogle Scholar
  56. Smith, G. D., and Peters, I. J., 1982, The localization in rat liver of alkaline phosphodiesterase to a discrete organelle implicated in ligand internalization, Biochim. Biophys. Acta 716: 24–30.PubMedCrossRefGoogle Scholar
  57. Stockera, W., and Wohlfarth-Botterman, K., 1969, Pinocytosis (endocytosis), in: “Handbook of Molecular Cytology”, A. Lima-de-Faria, ed., North Holland, Amsterdam, pp. 1373–1400Google Scholar
  58. Tycko, B., and Maxfield, F.R., 1982, Rapid acidification of endocytic vesicles containing 2-macroglobulin, Cell, 28: 643–651.PubMedCrossRefGoogle Scholar
  59. Wall, D. A., Wilson, G., and Hubbard, B., 1980, The galactose specific recognition system of mammalian liver: The route of ligand internalization in rat hepatocytes, Cell, 21: 79–93.PubMedCrossRefGoogle Scholar
  60. Walsh, R. J., Posner, B. I., and Patel, B., 1984, Binding and uptake of 125I-iodoprolactin by epithelial cells of the rat choroid plexus: An in vivo autoradiographic analysis, Endocrinology, 114: 1496–1505.PubMedCrossRefGoogle Scholar
  61. Willingham, M. C., and Pastan, I., 1980, The receptosome: An intermediate organelle of receptor-mediated endocytosis in cultured fibroblasts, Cell, 21: 67–77.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Barry I. Posner
    • 1
  • Masood N. Khan
    • 1
  • Denis G. Kay
    • 1
  • John J. M. Bergeron
    • 1
  1. 1.Departments of Medicine and AnatomyMcGill UniversityMontrealCanada

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