Mutant of Chinese Hamster Ovary Cells with Altered Mannose 6-phosphate Receptor Activity is Unable to Synthesize Mannosylphosphoryldolichol

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1982 Apr 1

PMID 6954541

Citations 28

Authors

J Stoll

A R ROBBINS

S S Krag

Affiliations

Soon will be listed here.

Abstract

B4-2-1 is a Chinese hamster ovary cell mutant previously isolated and characterized as deficient in mannose 6-phosphate receptor activity. We show here that B4-2-1 is a pleiotropic mutant, defective in biosynthesis of asparagine-linked oligosaccharides, B4-2-1 is unable to synthesize mannosylphosphoryldolichol; the consequences of this defect on glycosylation are (i) biosynthesis of one major lipid-linked oligosaccharide, characterized by its resistance to endoglycosidase H and decreased size; this oligosaccharide is similar to a minor species of lipid-liked oligosaccharide found in parental cells; (ii) transfer of this oligosaccharide to newly synthesized proteins; and (iii) absence of normal "high-mannose" oligosaccharides on mature glycoproteins isolated from B4-2-1; glycoproteins from the mutant contain complex oligosaccharides as well as endoglycosidase H-resistant, alpha-mannosidase-sensitive species. While the glycosylation defect may alter adversely the function of several glycoproteins in the mutant, including that of the mannose 6-phosphate receptor, it appears to have no effect on the formation or function of the mannose 6-phosphate recognition marker on acid hydrolases of B4-2-1.

Citing Articles

N-glycome of the Lysosomal Glycocalyx is Altered in Niemann-Pick Type C Disease (NPC) Model Cells.

Kosicek M, Gudelj I, Horvatic A, Jovic T, Vuckovic F, Lauc G Mol Cell Proteomics. 2018; 17(4):631-642.

PMID: 29367433 PMC: 5880104. DOI: 10.1074/mcp.RA117.000129.

Large induces functional glycans in an O-mannosylation dependent manner and targets GlcNAc terminals on alpha-dystroglycan.

Hu Y, Li Z, Wu X, Lu Q PLoS One. 2011; 6(2):e16866.

PMID: 21347376 PMC: 3036717. DOI: 10.1371/journal.pone.0016866.

Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells.

Jones M, Tomiya N, Betenbaugh M, Krag S Biochem Biophys Res Commun. 2010; 395(1):36-41.

PMID: 20331963 PMC: 2887678. DOI: 10.1016/j.bbrc.2010.03.117.

Disruption of mannose activation in Leishmania mexicana: GDP-mannose pyrophosphorylase is required for virulence, but not for viability.

Garami A, Ilg T EMBO J. 2001; 20(14):3657-66.

PMID: 11447107 PMC: 125538. DOI: 10.1093/emboj/20.14.3657.

Dolichol phosphate mannose synthase (DPM1) mutations define congenital disorder of glycosylation Ie (CDG-Ie).

Kim S, Westphal V, Srikrishna G, Mehta D, Peterson S, Filiano J J Clin Invest. 2000; 105(2):191-8.

PMID: 10642597 PMC: 377427. DOI: 10.1172/JCI7302.

References

Braell W, Tyo M, Krag S, Robbins P . A new procedure for the preparation of GDP-[U-14C]mannose. Anal Biochem. 1976; 74(2):484-7. DOI: 10.1016/0003-2697(76)90229-3. View

Krag S, Robbins P . Sindbis envelope proteins as endogenous acceptors in reactions of guanosine diphosphate-[14C]Mannose with preparations of infected chicken embryo fibroblasts. J Biol Chem. 1977; 252(8):2621-9. View

Sando G, Neufeld E . Recognition and receptor-mediated uptake of a lysosomal enzyme, alpha-l-iduronidase, by cultured human fibroblasts. Cell. 1977; 12(3):619-27. DOI: 10.1016/0092-8674(77)90262-8. View

Kobata A . endo-beta-N-Acetylglucosaminidases CI and CII from Clostridium perfringens. Methods Enzymol. 1978; 50:567-74. DOI: 10.1016/0076-6879(78)50064-5. View

von Figura K, Klein U . Isolation and characterization of phosphorylated oligosaccharides from alpha-N-acetylglucosaminidase that are recognized by cell-surface receptors. Eur J Biochem. 1979; 94(2):347-54. DOI: 10.1111/j.1432-1033.1979.tb12900.x. View

Li E, Kornfeld S . Biosynthesis of lipid-linked oligosaccharides. Isolation and structure of a second lipid-linked oligosaccharide in Chinese hamster ovary cells. J Biol Chem. 1979; 254(8):2754-8. View

Rome L, Weissmann B, Neufeld E . Direct demonstration of binding of a lysosomal enzyme, alpha-L-iduronidase, to receptors on cultured fibroblasts. Proc Natl Acad Sci U S A. 1979; 76(5):2331-4. PMC: 383594. DOI: 10.1073/pnas.76.5.2331. View

Trowbridge I, HYMAN R . Abnormal lipid-linked oligosaccharides in class E Thy-1-negative mutant lymphomas. Cell. 1979; 17(3):503-8. DOI: 10.1016/0092-8674(79)90258-7. View

Chapman A, Trowbridge I, HYMAN R, Kornfeld S . Structure of the lipid-linked oligosaccharides that accumulate in class E Thy-1-negative mutant lymphomas. Cell. 1979; 17(3):509-15. DOI: 10.1016/0092-8674(79)90259-9. View

10.

Krag S . A concanavalin A-resistant Chinese hamster ovary cell line is deficient in the synthesis of [3H]glucosyl oligosaccharide-lipid. J Biol Chem. 1979; 254(18):9167-77. View

11.

Distler J, Hieber V, Sahagian G, Schmickel R, JOURDIAN G . Identification of mannose 6-phosphate in glycoproteins that inhibit the assimilation of beta-galactosidase by fibroblasts. Proc Natl Acad Sci U S A. 1979; 76(9):4235-9. PMC: 411547. DOI: 10.1073/pnas.76.9.4235. View

12.

Natowicz M, Chi M, LOWRY O, Sly W . Enzymatic identification of mannose 6-phosphate on the recognition marker for receptor-mediated pinocytosis of beta-glucuronidase by human fibroblasts. Proc Natl Acad Sci U S A. 1979; 76(9):4322-6. PMC: 411566. DOI: 10.1073/pnas.76.9.4322. View

13.

Bach G, Bargal R, Cantz M . I-cell disease: deficiency of extracellular hydrolase phosphorylation. Biochem Biophys Res Commun. 1979; 91(3):976-81. DOI: 10.1016/0006-291x(79)91975-2. View

14.

Chapman A, Fujimoto K, Kornfeld S . The primary glycosylation defect in class E Thy-1-negative mutant mouse lymphoma cells is an inability to synthesize dolichol-P-mannose. J Biol Chem. 1980; 255(10):4441-6. View

15.

Hasilik A, Neufeld E . Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J Biol Chem. 1980; 255(10):4937-45. View

16.

Hasilik A, Neufeld E . Biosynthesis of lysosomal enzymes in fibroblasts. Phosphorylation of mannose residues. J Biol Chem. 1980; 255(10):4946-50. View

17.

Fischer H, Gonzalez-Noriega A, Sly W . Beta-glucuronidase binding to human fibroblast membrane receptors. J Biol Chem. 1980; 255(11):5069-74. View

18.

Tabas I, Kornfeld S . Biosynthetic intermediates of beta-glucuronidase contain high mannose oligosaccharides with blocked phosphate residues. J Biol Chem. 1980; 255(14):6633-9. View

19.

Gonzalez-Noriega A, Grubb J, Talkad V, Sly W . Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J Cell Biol. 1980; 85(3):839-52. PMC: 2111452. DOI: 10.1083/jcb.85.3.839. View

20.

Varki A, Kornfeld S . Structural studies of phosphorylated high mannose-type oligosaccharides. J Biol Chem. 1980; 255(22):10847-58. View