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Abstract:

Glucosidase I (GI) removes the outermost glucose from protein-linked Glc 3 Man 9 GlcNAc 2 (G3M9) in the endoplasmic reticulum (ER). Individuals with congenital disorders of glycosylation MOGS-CDG bear mutations in the GI-encoding gene (gls1). Although GI absence has been reported to produce lethality in Schizosaccharomyces pombe yeasts, here we obtained two viable gls1 mutants, one with a very sick but not lethal phenotype (gls1-S) and the other with a healthier one (gls1-H). The sick strain displayed only G3M9 as an ER protein–linked oligosaccharide, whereas the healthier strain had both G3M9 and Man 9 GlcNAc 2 . The lipid-linked oligosaccharide patterns of the two strains revealed that the most abundantly formed glycans were G3M9 in gls1-S and Glc 2 Man 9 GlcNAc 2 in gls1-H, suggesting reduced Alg10p glucosyltransferase activity in the gls1-H strain. A mutation in the alg10 gene was indeed observed in this strain. Our results indicated that abrogated G3M9 deglucosylation was responsible for the severe defects observed in gls1-S cells. Further studies disclosed that the defects could not be ascribed to disruption of glycoprotein entrance into calnexin-folding cycles, inhibition of the oligosaccharyltransferase by transfer reaction products, or reduced proteasomal degradation of misfolded glycoproteins. Lack of triglucosylated glycoprotein deglucosylation neither significantly prevented glycan elongation in the Golgi nor modified the overall cell wall monosaccharide composition. Nevertheless, it resulted in a distorted cell wall and in the absence of underlying ER membranes. Furthermore, Golgi expression of human endomannosidase partially restored normal growth in gls1-S cells. We propose that accumulation of G3M9-bearing glycoproteins is toxic and at least partially responsible for defects observed in MOGS-CDG. © 2018 Gallo et al.

Registro:

Documento: Artículo
Título:Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder
Autor:Gallo, G.L.; Valko, A.; Aramburu, S.I.; Etchegaray, E.; Völker, C.; Parodi, A.J.; D’Alessio, C.
Filiación:Fundación Instituto Leloir–IIBBA, CONICET, Buenos Aires, C1405BWE, Argentina
Institute of Biochemistry and Molecular Biology Medical Faculty, University of Bonn, Bonn, 53115, Germany
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Fundación Instituto Leloir, Av. Patricias Argentinas 435, Buenos Aires, C1405BWE, Argentina
Palabras clave:glucosidase; glucosidase I; glucosyltransferase; unclassified drug; Article; bioaccumulation; cell death; cell elongation; cellular distribution; chemical modification; conformation; congenital disorder of glycosylation; controlled study; deglucosylation; endoplasmic reticulum; enzyme activity; fungal cell; fungal cell wall; fungus growth; gene mutation; nonhuman; phenotype; priority journal; protein degradation; protein expression; protein folding; protein misfolding; Schizosaccharomyces pombe; transmission electron microscopy
Año:2018
Volumen:293
Número:52
Página de inicio:19957
Página de fin:19973
DOI: http://dx.doi.org/10.1074/jbc.RA118.004844
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:glucosidase, 9033-06-1; glucosyltransferase, 9031-48-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v293_n52_p19957_Gallo

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Citas:

---------- APA ----------
Gallo, G.L., Valko, A., Aramburu, S.I., Etchegaray, E., Völker, C., Parodi, A.J. & D’Alessio, C. (2018) . Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder. Journal of Biological Chemistry, 293(52), 19957-19973.
http://dx.doi.org/10.1074/jbc.RA118.004844
---------- CHICAGO ----------
Gallo, G.L., Valko, A., Aramburu, S.I., Etchegaray, E., Völker, C., Parodi, A.J., et al. "Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder" . Journal of Biological Chemistry 293, no. 52 (2018) : 19957-19973.
http://dx.doi.org/10.1074/jbc.RA118.004844
---------- MLA ----------
Gallo, G.L., Valko, A., Aramburu, S.I., Etchegaray, E., Völker, C., Parodi, A.J., et al. "Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder" . Journal of Biological Chemistry, vol. 293, no. 52, 2018, pp. 19957-19973.
http://dx.doi.org/10.1074/jbc.RA118.004844
---------- VANCOUVER ----------
Gallo, G.L., Valko, A., Aramburu, S.I., Etchegaray, E., Völker, C., Parodi, A.J., et al. Abrogation of glucosidase I–mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder. J. Biol. Chem. 2018;293(52):19957-19973.
http://dx.doi.org/10.1074/jbc.RA118.004844