Abstract
Proteases were initially identified in endosomes through studies of receptor-ligand transport.1 During receptor-mediated endocytosis, cell surface receptors bind exogenous ligands (Figure 1). These receptor-ligand complexes are internalized by clathrin-coated vesicles, which give rise to endosomes. Shortly after endosome formation, the internal pH of these vesicles drops to between pH 5–6.2 Many internalized receptor-ligand complexes dissociate upon endosome acidification, with the released receptors recycling back to the cell surface. Ligands delivered into endosomes undergo a variety of fates including transport back to the cell surface3 or sorting to different intracellular compartments such as lysosomes and the Golgi.4,5 Susceptible protein ligands are cleaved in endosomes indicating that these vesicles also serve as a processing compartment.1,6,8
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References
S. Diment and P. Stahl, Macrophage endosomes contain proteases which degrade endocytosed protein ligands, J. Biol Chem. 260: 15311 (1985).
B. Tycko and F. R. Maxfield, Rapid acidification of endocytic vesicles containing α2-macroglobulin, Cell 28: 643 (1982).
C. Tietze, P. Schlesinger and P. Stahl, Mannose-specific endocytosis receptor of alveolar macrophages: Demonstration of two functionally distinct intracellular pools of receptor and their role in receptor recycling, J. Cell Biol. 92: 417 (1982).
J. L. Goldstein, R. G. W. Anderson and M. S. Brown, Coated pits, coated vesicles and receptor-mediated endocytosis, Nature 279: 679 (1979).
M. D. Snider and O. C. Rogers, Intracellular movement of cell surface receptors after endocytosis: Resialylation of asialo-transferrin receptor in human erythroleukemia cells, J. Cell Biol 100: 826 (1985).
M. Roederer, R. Bowser and R. F. Murphy, Kinetics and temperature dependence of exposure of endocytosed material to proteolytic enzymes of low pH: Evidence for a maturation model for the formation of lysosomes, J. Cell Physiol. 131: 200 (1987).
F. G. Hamel, B. I. Posner, J. J. M. Bergeron, B. H. Frank and W. C. Duckworth, Isolation of insulin degradation products from endosomes derived from intact rat liver, J. Biol. Chem. 263: 6703 (1988).
J. S. Blum, R. Diaz, S. Diment, M. Fiani, L. Mayorga, J. S. Rodman, P. D. Stahl, Proteolytic processing in endosomal vesicles, Cold Spring Harbor Symposia on Quantitative Biology 54: 287 (1989).
P. Stahl, P. Schlesinger, E. Sigardson, J. S. Rodman and Y. C. Lee, Receptor-mediated pinocytosis of mannose glycoconjugates by macrophages: Characterization and evidence for receptor recycling, Cell 19: 207 (1980).
T. Wileman, R. L. Boshans, P. Schlesinger and P. Stahl, Monensin inhibits recycling of macrophages and ligand delivery to lysosomes, Biochem. J. 220: 665 (1984).
J. S. Blum, M. L. Fiani and P. D. Stahl, Characterization of neutral and acidic proteases in endosomal vesicles, J. Cell Biol. 109: 188a (1989).
A. Hasilik and E. F. Neufeld, Biosynthesis of lysosomal enzymes in fibroblasts, J. Biol. Chem. 255: 4937 (1980).
S. Diment, M. Leech and P. Stahl, Cathepsin D is membrane-associated in macrophage endosomes, J. Biol. Chem. 263: 6901 (1988).
S. Kornfeld and I. Mellman, The biogenesis of lysosomes, Annu. Rev. Cell Biol. 5: 483 (1989).
G. Griffiths, B. Hoflack, K. Simons, I. Mellman and S. Kornfeld, The mannose-6-phosphate receptor and the biogenesis of lysosomes, Cell 52: 329 (1988).
T. Braulke, H. J. Geuze, J. W. Slot, A. Hasilik and K. von Figura, On the effects of weak bases and monensin on sorting and processing of lysosomal enzymes in human cells, Eur. J. Cell Biol. 43: 316 (1987).
J. S. Rodman, M. A. Levy, S. Diment and P. D. Stahl, Immunolocalization of endosomal cathepsin D in rabbit aveolar macrophages, J. Leuk. Biol. 48: 116 (1990).
L. E. Guagliardi, B. Koppelman, J. S. Blum, M. S. Marks, P. Cresswell and F. M. Brodsky, Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment, Nature 343: 133 (1990).
S. Diment, K. Martin and P. Stahl, Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins, J. Biol. Chem. 264: 13403 (1989).
K. L. McCoy and R. H. Schwartz, The role of intracellular acidification in antigen processing, Immunol. Rev. 106: 129 (1988).
E. R. Unanue and P. M. Allen, The basis for the immunoregulatory role of macrophages and other accessory cells, Science 236: 551 (1987).
J. Puri and Y. Factorovich, Selective inhibition of antigen presentation to cloned T cells by protease inhibitors, J. Immunol. 141: 3313 (1988).
H. Takahashi, K. B. Clase and J. A. Berzofsky, Identification of proteases that process distinct epitopes on the protein, J. Immunol. 142: 2221 (1989).
J. M. van Noort and A. C. M. van der Drift, The selectivity of cathepsin D suggests an involvement of the enzyme in the generation of T-cell epitopes, J. Biol. Chem. 264: 14159 (1989).
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© 1991 Plenum Press, New York
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Blum, J.S., Fiani, M.L., Stahl, P.D. (1991). Localization of Cathepsin D in Endosomes: Characterization and Biological Importance. In: Dunn, B.M. (eds) Structure and Function of the Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 306. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6012-4_34
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DOI: https://doi.org/10.1007/978-1-4684-6012-4_34
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