Mannosamine, a Novel Inhibitor of Glycosylphosphatidylinositol Incorporation into Proteins

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1991 Aug 1

PMID 1829673

Citations 26

Authors

M P Lisanti

M C Field

I W Caras

A K Menon

E Rodriguez-Boulan

Affiliations

Soon will be listed here.

Abstract

Mannosamine (2-amino-2-deoxy D-mannose) is shown here to block the incorporation of glycosylphosphatidylinositol (GPI) into GPI-anchored proteins. The amino sugar drastically reduced the surface expression of a recombinant GPI-anchored protein in polarized MDCK cells, converted this apical membrane-bound protein to an unpolarized secretory product and blocked the expression of endogenous GPI-anchored proteins. Furthermore, it specifically inhibited the incorporation of [3H]ethanolamine (a GPI component) into mammalian and trypanosomal GPI-anchored proteins and into a well characterized GPI-lipid of Trypanosoma brucei. These results suggest that mannosamine converted an apical GPI-anchored protein to a non-polarized secretory product by depleting transfer competent GPI-precursor lipids. Our inhibitor studies provide new independent evidence for the apical targeting role of GPI in polarized epithelia and open the way towards a greater understanding of the functional role of GPI in membrane trafficking and cell regulation.

Citing Articles

Biological Role of the Intercellular Transfer of Glycosylphosphatidylinositol-Anchored Proteins: Stimulation of Lipid and Glycogen Synthesis.

Muller G, Muller T Int J Mol Sci. 2022; 23(13).

PMID: 35806423 PMC: 9267055. DOI: 10.3390/ijms23137418.

Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes.

Friedes B, Molloy E, Strickland T, Zhu J, Slevin M, Donoghue V Pediatr Res. 2021; 92(2):466-473.

PMID: 34621028 PMC: 8986879. DOI: 10.1038/s41390-021-01741-x.

LY6K promotes glioblastoma tumorigenicity via CAV-1-mediated ERK1/2 signaling enhancement.

Sastry N, Wan X, Huang T, Alvarez A, Pangeni R, Song X Neuro Oncol. 2020; 22(9):1315-1326.

PMID: 32055849 PMC: 7523463. DOI: 10.1093/neuonc/noaa032.

Glycosylphosphatidylinositol (GPI) Modification Serves as a Primary Plasmodesmal Sorting Signal.

Zavaliev R, Dong X, Epel B Plant Physiol. 2016; 172(2):1061-1073.

PMID: 27559035 PMC: 5047108. DOI: 10.1104/pp.16.01026.

PrP-containing aggresomes are cytosolic components of an ER quality control mechanism.

Dubnikov T, Ben-Gedalya T, Reiner R, Hoepfner D, Cabral W, Marini J J Cell Sci. 2016; 129(19):3635-3647.

PMID: 27550517 PMC: 6518310. DOI: 10.1242/jcs.186981.

References

Ferguson M, Duszenko M, Lamont G, Overath P, Cross G . Biosynthesis of Trypanosoma brucei variant surface glycoproteins. N-glycosylation and addition of a phosphatidylinositol membrane anchor. J Biol Chem. 1986; 261(1):356-62. View

Rodriguez-Boulan E . Polarized assembly of enveloped viruses from cultured epithelial cells. Methods Enzymol. 1983; 98:486-501. DOI: 10.1016/0076-6879(83)98176-4. View

Takami N, Ogata S, Oda K, Misumi Y, Ikehara Y . Biosynthesis of placental alkaline phosphatase and its post-translational modification by glycophospholipid for membrane-anchoring. J Biol Chem. 1988; 263(6):3016-21. View

Green R, Meiss H, Rodriguez-Boulan E . Glycosylation does not determine segregation of viral envelope proteins in the plasma membrane of epithelial cells. J Cell Biol. 1981; 89(2):230-9. PMC: 2111687. DOI: 10.1083/jcb.89.2.230. View

Reggio H, Webster P, Louvard D . Use of immunocytochemical techniques in studying the biogenesis of cell surfaces in polarized epithelia. Methods Enzymol. 1983; 98:379-95. DOI: 10.1016/0076-6879(83)98166-1. View

Meiss H, Green R . Lectin-resistant mutants of polarized epithelial cells. Mol Cell Biol. 1982; 2(10):1287-94. PMC: 369928. DOI: 10.1128/mcb.2.10.1287-1294.1982. View

Pan Y, Elbein A . The formation of lipid-linked oligosaccharides in Madin-Darby canine kidney cells. Changes in oligosaccharide profiles induced by glucosamine. J Biol Chem. 1982; 257(6):2795-801. View

Chamberlain J . Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979; 98(1):132-5. DOI: 10.1016/0003-2697(79)90716-4. View

Schneider P, Ferguson M, McConville M, Mehlert A, Homans S, Bordier C . Structure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease. J Biol Chem. 1990; 265(28):16955-64. View

10.

Powell S, Lisanti M . Thy-1 expresses two signals for apical localization in epithelial cells. Am J Physiol. 1991; 260(4 Pt 1):C715-20. DOI: 10.1152/ajpcell.1991.260.4.C715. View

11.

Dotti C, Parton R, Simons K . Polarized sorting of glypiated proteins in hippocampal neurons. Nature. 1991; 349(6305):158-61. DOI: 10.1038/349158a0. View

12.

Moran P, Raab H, Kohr W, Caras I . Glycophospholipid membrane anchor attachment. Molecular analysis of the cleavage/attachment site. J Biol Chem. 1991; 266(2):1250-7. View

13.

deGasperi R, Thomas L, Sugiyama E, Chang H, Beck P, Orlean P . Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene. Science. 1990; 250(4983):988-91. DOI: 10.1126/science.1978413. View

14.

Cross G . Glycolipid anchoring of plasma membrane proteins. Annu Rev Cell Biol. 1990; 6:1-39. DOI: 10.1146/annurev.cb.06.110190.000245. View

15.

Fatemi S, Tartakoff A . Hydrophilic anchor-deficient Thy-1 is secreted by a class E mutant T lymphoma. Cell. 1986; 46(5):653-7. DOI: 10.1016/0092-8674(86)90340-5. View

16.

Conzelmann A, Spiazzi A, HYMAN R, Bron C . Anchoring of membrane proteins via phosphatidylinositol is deficient in two classes of Thy-1 negative mutant lymphoma cells. EMBO J. 1986; 5(12):3291-6. PMC: 1167325. DOI: 10.1002/j.1460-2075.1986.tb04642.x. View

17.

Hooper N, Turner A . Ectoenzymes of the kidney microvillar membrane. Differential solubilization by detergents can predict a glycosyl-phosphatidylinositol membrane anchor. Biochem J. 1988; 250(3):865-9. PMC: 1148935. DOI: 10.1042/bj2500865. View

18.

Menon A, Mayor S, Schwarz R . Biosynthesis of glycosyl-phosphatidylinositol lipids in Trypanosoma brucei: involvement of mannosyl-phosphoryldolichol as the mannose donor. EMBO J. 1990; 9(13):4249-58. PMC: 552207. DOI: 10.1002/j.1460-2075.1990.tb07873.x. View

19.

Lisanti M, Caras I, Gilbert T, Hanzel D, Rodriguez-Boulan E . Vectorial apical delivery and slow endocytosis of a glycolipid-anchored fusion protein in transfected MDCK cells. Proc Natl Acad Sci U S A. 1990; 87(19):7419-23. PMC: 54758. DOI: 10.1073/pnas.87.19.7419. View

20.

Bailey C, Gerber L, Howard A, UDENFRIEND S . Processing at the carboxyl terminus of nascent placental alkaline phosphatase in a cell-free system: evidence for specific cleavage of a signal peptide. Proc Natl Acad Sci U S A. 1989; 86(1):22-6. PMC: 286395. DOI: 10.1073/pnas.86.1.22. View