A novel fission yeast platform to model N-glycosylation and the bases of congenital disorders of glycosylation type I

被引:7
作者
Gallo, Giovanna L. [1 ,2 ,3 ,4 ]
Valko, Ayelen [1 ,2 ,3 ]
Herrera Aguilar, Nathalia [1 ,3 ]
Weisz, Ariel D. [1 ]
D'Alessio, Cecilia [1 ,2 ]
机构
[1] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Inst Biociencias Biotecnol & Biol Traslac iB3, Dept Fisiol Biol Mol & Celular, C1428EGA, Buenos Aires, DF, Argentina
[2] Consejo Nacl Invest Cient & Tecn, C1425FQB, Buenos Aires, DF, Argentina
[3] Fdn Inst Leloir, C1405BWE, Buenos Aires, DF, Argentina
[4] Consejo Nacl Invest Cient & Tecn, Ctr Virol Humana & Anim CEVHAN, C1440FFX, Buenos Aires, DF, Argentina
关键词
ALG genes; Congenital disorders of glycosylation; Endoplasmic reticulum; Hypoglycosylation; Lipid-linked oligosaccharide; N-glycosylation; Oligosaccharyltransferase; Schizosaccharomyces pombe; Yeast; DOLICHOL-LINKED OLIGOSACCHARIDE; OLIGOSACCHARYLTRANSFERASE COMPLEX; PROTEIN GLYCOSYLATION; GLYCOPROTEIN GLUCOSYLTRANSFERASE; SCHIZOSACCHAROMYCES-POMBE; GLUCOSE STARVATION; GLYCAN; DEFICIENCY; MUTATIONS; PROVIDES;
D O I
10.1242/jcs.259167
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Congenital disorders of glycosylation type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe strains that synthesize all possible theoretical combinations of LLOs containing three to zero glucose (Glc) residues and nine to five mannose (Man) residues. The occurrence of unexpected LLOs suggested the requirement of specific Man residues for glucosyltransferase activities. We then quantified protein hypoglycosylation in each strain and found that in S. pombe the presence of Glc in the LLO is more relevant to the transfer efficiency than the number of Man residues. Surprisingly, a decrease in the number of Man residues in glycans somehow improved the glycan transfer. The most severe hypoglycosylation was produced in cells that synthesized LLOs completely lacking Glc and having a high number of Man residues. This deficiency could be reverted by expressing a single-subunit oligosaccharyltransferase with a broad range of substrate specificity. Our work shows the usefulness of this new S. pombe set of mutants as a platform to model the molecular bases of human CDG-I diseases. This article has an associated First Person interview with the first authors of the paper.
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页数:13
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