Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis.

Damme M, Morelle W, Schmidt B, Andersson C, Fogh J, Michalski J-C, Lübke T (2010)
Molecular and Cellular Biology 30(1): 273-283.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Damme, MarkusUniBi; Morelle, Willy; Schmidt, Bernhard; Andersson, Claes; Fogh, Jens; Michalski, Jean-Claude; Lübke, TorbenUniBi
Abstract / Bemerkung
Alpha-mannosidosis is caused by the genetic defect of the lysosomal alpha-d-mannosidase (LAMAN), which is involved in the breakdown of free alpha-linked mannose-containing oligosaccharides originating from glycoproteins with N-linked glycans, and thus manifests itself in an extensive storage of mannose-containing oligosaccharides. Here we demonstrate in a model of mice with alpha-mannosidosis that native lysosomal proteins exhibit elongated N-linked oligosaccharides as shown by two-dimensional difference gel electrophoresis, deglycosylation assays, and mass spectrometry. The analysis of cathepsin B-derived oligosaccharides revealed a hypermannosylation of glycoproteins in mice with alpha-mannosidosis as indicated by the predominance of extended Man3GlcNAc2 oligosaccharides. Treatment with recombinant human alpha-mannosidase partially corrected the hyperglycosylation of lysosomal proteins in vivo and in vitro. These data clearly demonstrate that LAMAN is involved not only in the lysosomal catabolism of free oligosaccharides but also in the trimming of asparagine-linked oligosaccharides on native lysosomal proteins.
Erscheinungsjahr
2010
Zeitschriftentitel
Molecular and Cellular Biology
Band
30
Ausgabe
1
Seite(n)
273-283
ISSN
0270-7306
Page URI
https://pub.uni-bielefeld.de/record/1902203

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Damme M, Morelle W, Schmidt B, et al. Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular and Cellular Biology. 2010;30(1):273-283.
Damme, M., Morelle, W., Schmidt, B., Andersson, C., Fogh, J., Michalski, J. - C., & Lübke, T. (2010). Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular and Cellular Biology, 30(1), 273-283. doi:10.1128/MCB.01143-09
Damme, M., Morelle, W., Schmidt, B., Andersson, C., Fogh, J., Michalski, J. - C., and Lübke, T. (2010). Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular and Cellular Biology 30, 273-283.
Damme, M., et al., 2010. Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular and Cellular Biology, 30(1), p 273-283.
M. Damme, et al., “Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis.”, Molecular and Cellular Biology, vol. 30, 2010, pp. 273-283.
Damme, M., Morelle, W., Schmidt, B., Andersson, C., Fogh, J., Michalski, J.-C., Lübke, T.: Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis. Molecular and Cellular Biology. 30, 273-283 (2010).
Damme, Markus, Morelle, Willy, Schmidt, Bernhard, Andersson, Claes, Fogh, Jens, Michalski, Jean-Claude, and Lübke, Torben. “Impaired lysosomal trimming of N-linked oligosaccharides leads to hyperglycosylation of native lysosomal proteins in mice with alpha-mannosidosis.”. Molecular and Cellular Biology 30.1 (2010): 273-283.

13 Zitationen in Europe PMC

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