Abstract
Receptor-mediated endocytosis is the process used by all eukaryotic cells to internalize a variety of biologically important macromolecules, e.g., transport proteins that deliver nutrients to cells (1,2), plasma proteins (3), hormones and growth factors (4,5), and lysosomal enzymes (6). The process is initiated when cell surface proteins (receptors) bind specific macromolecules (ligands) with high affinity at the plasma membrane. Following ligand binding, receptor-ligand complexes are rapidly internalized through clathrin-coated pits and delivered to endosomes. In endosomes, sorting and segregation of ligands and receptors into one of several pathways occur (7). For example, some receptors recycle to the cell surface while their ligands are degraded to amino acids in lysosomes, whereas in other cases, both are degraded or recycled. In hepatocytes, receptors and ligand may also be transported across the cell via a process called transcytosis.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Brown, M. S. and Goldstein J. L. (1976) Receptor-mediated control of cholesterol metabolism. Science 191, 150–154.
Hopkins, C. R. and Trowbridge, I. S. (1983) Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells. J. Cell Biol. 97, 508–521.
Wall, D. A, Wilson, G, and Hubbard, A L. (1980) The galactose-specific recognition system of mammalian liver: the route of ligand internalization in rat hepatocytes. Cell 21, 79–93
Dunn, W. A. and Hubbard, A. L (1984) Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver ligand and receptor dynamics. J. Cell Biol. 98, 2148–2159.
Krupp, M. N. and Lane, M. D. (1982) Evidence for different pathways of insulin and insulin receptor in the chick liver cell. J. Biol. Chem. 257, 1372–1377.
Braulke, T., Gartung, C. Hasilik, A., and von Figura, K. (1987) Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes? J. Cell Biol 104, 1735–1742.
Helenius, A., Mellman, I., Wall, D., and Hubbard, A. (1983) Endosomes. Trends Biochem. Sct. 8, 245–250.
Diment, S. and Stahl, P. D. (1985) Macrophage endosomes contain proteases which degrade endocytosed protein ligands. J. Biol. Chem. 260, 15,311–15,317
Lippincott-Schwartz, J. L. and Fambrough, D, M. (1987) Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lyso-somes’ kinetic and morphologic analysis. Cell 49, 669–677.
Dunn, W. A., Hubbard, A. L., and Aronson, N. N., Jr. (1980) Low temperature selectively inhibits fusion between pmocytic vesicles and lysosomes during heterophagy of 125I-asialofetuin by the perfused rat liver. J. Biol. Chem. 255, 5971–5978.
Hubbard, A. L, Wilson, G., Ashwell, G., and Stukenbrok, H. (1979) An electron microscope autoradiographic study of the carbohydrate recognition systems in rat liver. L Distribution of 125I-ligands among the liver cell types. J. Cell Biol. 83, 47–64.
Dunn, W. A, Wall, D. A., and Hubbard, A. L. (1983) Use of isolated perfused liver in studies of receptor-mediated endocytosis. Methods Enzymol 98, 225–240.
Doherty, J-J. II, Kay, D. G., Lai, W. H., Posner, B. I, and Bergeron, J. J. M. (1990) Selective degradation of insulin within rat liver endosomes. J. Cell Biol. 110, 35–42
Casciola-Rosen, L. A. F. and Hubbard, A. L. (1991) Hydrolases in intracellular compartments of rat liver cells: evidence for differential activation and/or delivery. J. Biol. Chem. 266, 4341–4347.
Clarke, B. L. and Weigel, P. H. (1985) Recycling of the asialoglycoprotein receptor in isolated rat hepatocytes. J. Biol. Chem. 260, 128–133.
Renfrew, C. A. and Hubbard, A L. (1990) Sequential processing of epidermal growth factor in early and late endosomes of rat liver. J. Biol Chem. 266, 4348–4356.
Sell, S., Linthicum, D. S., Bass, D., Bahu, R., Wilson, B., and Nakane, P. (1977) in Advances in Pathobiology. Differentiation and Carcinogenesis, vol. IV (Borek, C, Fenoglio, C. M, and King, D W, eds), Stratton Intercontinental Medical Book Corp., New York, pp. 272–305.
Dunn, W. A., Connolly, T. P., and Hubbard, A. L (1986) Receptor-mediated endocytosis of epidermal growth factor by rat hepatocytes: receptor pathway. J Cell Biol. 102, 24–36.
Wall, D. A. and Hubbard, A. L. (1985) Receptor-mediated endocytosis of asialoglycoproteins by rat liver hepatocytes: biochemical characterization of the endosomal compartments. J. Cell Biol. 101, 2104–2112.
Cuatrecasas, P. (1972) Isolation of the insulin receptor of liver and fat-cell membranes. Proc. Natl. Acad. Sci. USA 69, 318–322.
Weigel, P. H. and Oka, J. A. (1983) The large intracellular pool of asialoglycoprotein receptors functions during the endocytosis of asialoglycoproteins by isolated rat hepatocytes. J Biol. Chem. 258, 5095–5102
Geuze, H. J., Slot, J. W., Strous, G. J. A. M., Lodish, H. F., and Schwartz, A L. (1983) Intracellular site of asialoglycoprotein receptor-ligand uncoupling double-label immunoelectron microscopy during receptor-mediated endocytosis. Cell 32, 277–287.
Matrisian, L. M., Planck, S. R., Finch, J. S., and Magnun, B. E. (1985) Heterogeneity of 125I-labeled epidermal growth factor. Biochim. Biophys. Acta 839, 139–146.
La Badie, J. H., Peterson-Chapman, K., and Aronson, N. N., Jr. (1975) Glycoprotein catabolism in rat liver. Biochem. J. 152, 271–279.
Canterbury, J. M., Bricker, L. A., Levey, G. S., Kozlovskis, P. L., Ruiz, E., ZuU, J. E., and Reiss, E. (1975) Metabolism of bovine parathyroid hormone Immunological and biological characteristics of fragments generated by liver perfusion. J. Clin. Invest. 55, 1245–1253.
Knook, D. L. and Sleyster, E. Ch. (1976) Separation of Kupffer and endothelial cells of the rat liver by centrifugal elutriation. Exp. Cell Res. 99, 444–449.
Borden, L. A., Einstein, R., Gabel, C. A., and Maxfield, F. R. (1990) Acidification-dependent dissociation of endocytosed insulin precedes that of endo-cytosed protein bearing the mannose 6-phosphate recognition marker. J. Biol. Chem. 265, 8497–8504
Munson, P. J. and Rodbard, D. (1980) Ligand: a versatile computerized approach for characterization of ligand-binding systems Anal. Biochem. 107, 222–239.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1994 Humana Press Inc. Totowa, NJ
About this protocol
Cite this protocol
Renfrew, C.A., Casciola-Rosen, L.A., Hubbard, A.L. (1994). Ligand Binding and Processing. In: Biomembrane Protocols. Methods in Molecular Biology, vol 27. Springer, Totowa, NJ. https://doi.org/10.1385/0-89603-250-7:325
Download citation
DOI: https://doi.org/10.1385/0-89603-250-7:325
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-250-7
Online ISBN: 978-1-59259-514-3
eBook Packages: Springer Protocols