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. 1990 Nov;9(11):3507–3513. doi: 10.1002/j.1460-2075.1990.tb07559.x

Mannose 6-phosphate receptor dependent secretion of lysosomal enzymes.

H H Chao 1, A Waheed 1, R Pohlmann 1, A Hille 1, K von Figura 1
PMCID: PMC552099  PMID: 2170115

Abstract

BHK and mouse L cells transfected with the cDNA for the human 46 kd mannose 6-phosphate receptor (MPR 46) secrete excessive amounts of newly synthesized mannose 6-phosphate containing polypeptides. The secretion is dependent on the amount, the recycling and the affinity for ligands of MPR 46. Incubation of transfected cells with antibodies blocking the binding site of MPR 46 reduces the secretion, and cotransfection with the cDNA for the human 300 kd mannose 6-phosphate (MPR 300) restores it to normal values. These results indicate that the two mannose 6-phosphate receptors compete for binding of newly synthesized ligands. In contrast to ligands bound to MPR 300, those bound to the MPR 46 are transported to and released at a site, e.g. early endosomes or plasma membrane, from where they can exit into the medium. Since antibodies blocking the binding site of MPR 46 reduce secretion also in non-transfected BHK and mouse L cells, at least part of the basal secretion of M6P-containing polypeptides is mediated by the endogenous MPR 46.

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Selected References

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  1. Bernard H. U., Krämmer G., Röwekamp W. G. Construction of a fusion gene that confers resistance against hygromycin B to mammalian cells in culture. Exp Cell Res. 1985 May;158(1):237–243. doi: 10.1016/0014-4827(85)90446-x. [DOI] [PubMed] [Google Scholar]
  2. Besterman J. M., Airhart J. A., Woodworth R. C., Low R. B. Exocytosis of pinocytosed fluid in cultured cells: kinetic evidence for rapid turnover and compartmentation. J Cell Biol. 1981 Dec;91(3 Pt 1):716–727. doi: 10.1083/jcb.91.3.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bleekemolen J. E., Stein M., von Figura K., Slot J. W., Geuze H. J. The two mannose 6-phosphate receptors have almost identical subcellular distributions in U937 monocytes. Eur J Cell Biol. 1988 Dec;47(2):366–372. [PubMed] [Google Scholar]
  4. Braulke T., Gartung C., Hasilik A., von Figura K. Is movement of mannose 6-phosphate-specific receptor triggered by binding of lysosomal enzymes? J Cell Biol. 1987 Jun;104(6):1735–1742. doi: 10.1083/jcb.104.6.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Braulke T., Tippmer S., Chao H. J., von Figura K. Regulation of mannose 6-phosphate/insulin-like growth factor II receptor distribution by activators and inhibitors of protein kinase C. Eur J Biochem. 1990 May 20;189(3):609–616. doi: 10.1111/j.1432-1033.1990.tb15529.x. [DOI] [PubMed] [Google Scholar]
  6. Dahms N. M., Lobel P., Kornfeld S. Mannose 6-phosphate receptors and lysosomal enzyme targeting. J Biol Chem. 1989 Jul 25;264(21):12115–12118. [PubMed] [Google Scholar]
  7. Gabel C. A., Goldberg D. E., Kornfeld S. Identification and characterization of cells deficient in the mannose 6-phosphate receptor: evidence for an alternate pathway for lysosomal enzyme targeting. Proc Natl Acad Sci U S A. 1983 Feb;80(3):775–779. doi: 10.1073/pnas.80.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gartung C., Braulke T., Hasilik A., von Figura K. Internalization of blocking antibodies against mannose-6-phosphate specific receptors. EMBO J. 1985 Jul;4(7):1725–1730. doi: 10.1002/j.1460-2075.1985.tb03842.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hoflack B., Fujimoto K., Kornfeld S. The interaction of phosphorylated oligosaccharides and lysosomal enzymes with bovine liver cation-dependent mannose 6-phosphate receptor. J Biol Chem. 1987 Jan 5;262(1):123–129. [PubMed] [Google Scholar]
  10. Kornfeld S., Mellman I. The biogenesis of lysosomes. Annu Rev Cell Biol. 1989;5:483–525. doi: 10.1146/annurev.cb.05.110189.002411. [DOI] [PubMed] [Google Scholar]
  11. Morgan D. O., Edman J. C., Standring D. N., Fried V. A., Smith M. C., Roth R. A., Rutter W. J. Insulin-like growth factor II receptor as a multifunctional binding protein. Nature. 1987 Sep 24;329(6137):301–307. doi: 10.1038/329301a0. [DOI] [PubMed] [Google Scholar]
  12. Oshima A., Nolan C. M., Kyle J. W., Grubb J. H., Sly W. S. The human cation-independent mannose 6-phosphate receptor. Cloning and sequence of the full-length cDNA and expression of functional receptor in COS cells. J Biol Chem. 1988 Feb 15;263(5):2553–2562. [PubMed] [Google Scholar]
  13. Stein C., Gieselmann V., Kreysing J., Schmidt B., Pohlmann R., Waheed A., Meyer H. E., O'Brien J. S., von Figura K. Cloning and expression of human arylsulfatase A. J Biol Chem. 1989 Jan 15;264(2):1252–1259. [PubMed] [Google Scholar]
  14. Stein M., Zijderhand-Bleekemolen J. E., Geuze H., Hasilik A., von Figura K. Mr 46,000 mannose 6-phosphate specific receptor: its role in targeting of lysosomal enzymes. EMBO J. 1987 Sep;6(9):2677–2681. doi: 10.1002/j.1460-2075.1987.tb02559.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tong P. Y., Kornfeld S. Ligand interactions of the cation-dependent mannose 6-phosphate receptor. Comparison with the cation-independent mannose 6-phosphate receptor. J Biol Chem. 1989 May 15;264(14):7970–7975. [PubMed] [Google Scholar]
  16. Waheed A., Gottschalk S., Hille A., Krentler C., Pohlmann R., Braulke T., Hauser H., Geuze H., von Figura K. Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes in transfected baby hamster kidney cells. EMBO J. 1988 Aug;7(8):2351–2358. doi: 10.1002/j.1460-2075.1988.tb03079.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wendland M., Hille A., Nagel G., Waheed A., von Figura K., Pohlmann R. Synthesis of a truncated Mr 46,000 mannose 6-phosphate receptor that is secreted and retains ligand binding. Biochem J. 1989 May 15;260(1):201–206. doi: 10.1042/bj2600201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wileman T., Harding C., Stahl P. Receptor-mediated endocytosis. Biochem J. 1985 Nov 15;232(1):1–14. doi: 10.1042/bj2320001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. von Figura K., Hasilik A. Lysosomal enzymes and their receptors. Annu Rev Biochem. 1986;55:167–193. doi: 10.1146/annurev.bi.55.070186.001123. [DOI] [PubMed] [Google Scholar]

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