The Lec23 Chinese hamster ovary mutant is a sensitive host for detecting mutations in alpha-glucosidase I that give rise to congenital disorder of glycosylation IIb (CDG IIb)

The Journal of Biological Chemistry
Yeongjin HongPamela Stanley

Abstract

Lec23 Chinese hamster ovary cells are defective in alpha-glucosidase I activity, which removes the distal alpha(1,2)-linked glucose residue from Glc(3)Man(9)GlcNAc(2) moieties attached to glycoproteins in the endoplasmic reticulum. Mutations in the human GCS1 gene give rise to the congenital disorder of glycosylation termed CDG IIb. Lec23 mutant cells have been shown to alter lectin binding and to synthesize predominantly oligomannosyl N-glycans on endogenous glycoproteins. A single point mutation (TCC to TTC; Ser to Phe) was identified in Lec23 Gcs1 cDNA and genomic DNA. Serine at the analogous position is highly conserved in all GCS1 gene homologues. A human GCS1 cDNA reverted the Lec23 phenotype, whereas GCS1 cDNA carrying the lec23 mutation (S440F in human) did not. By contrast, GCS1 cDNA with an R486T or F652L CDG IIb mutation gave substantial rescue of the Lec23 phenotype. Nevertheless, in vitro assays of each enzyme gave no detectable alpha-glucosidase I activity. Clearly the R486T and F652L GCS1 mutations are only mildly debilitating in an intact cell, whereas the S440F mutation largely inactivates alpha-glucosidase I both in vitro and in vivo. However, the S440F alpha-glucosidase I may have a small amount of alpha-gluc...Continue Reading

References

Feb 1, 1992·Glycobiology·F A Troy
Apr 1, 1992·Glycobiology·P Stanley
May 1, 1990·Somatic Cell and Molecular Genetics·P StanleyB Dunn
May 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·J D EskoW H Taylor
Jan 1, 1985·Annual Review of Biochemistry·R Kornfeld, S Kornfeld
Jan 1, 1984·Annual Review of Genetics·P Stanley
Feb 23, 1995·Nature·M EckhardtR Gerardy-Schahn
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M EckhardtR Gerardy-Schahn
Aug 1, 1998·The Journal of Biological Chemistry·M EckhardtR Gerardy-Schahn
May 2, 2000·American Journal of Human Genetics· De Praeter CM Van Coster RN
Mar 28, 2001·Science·A Helenius, M Aebi
Jun 4, 2002·Glycobiology·Nancy B Schwartz, Miriam Domowicz
Nov 6, 2002·Biochimica Et Biophysica Acta·Hudson H Freeze
May 9, 2003·Glycobiology·Paul T Martin, Hudson H Freeze
Dec 4, 2003·Biological & Pharmaceutical Bulletin·Tamao Endo, Tatsushi Toda
Jul 27, 2004·Journal of Inherited Metabolic Disease·J Jaeken

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Citations

May 26, 2009·The Journal of Biological Chemistry·Max CrispinSimon J Davis
Mar 19, 2008·The Journal of Biological Chemistry·Mark StahlPamela Stanley
Sep 18, 2009·Glycobiology·Tania TorossiMartin Ziak
Nov 13, 2007·Seminars in Cell & Developmental Biology·Julio J Caramelo, Armando J Parodi
Feb 22, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yong LiuYanping Zhang
Jan 21, 2012·Chembiochem : a European Journal of Chemical Biology·Wesley F ZandbergB Mario Pinto
Apr 6, 2006·Seminars in Pediatric Neurology·Erik A Eklund, Hudson H Freeze

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