Glycosylation network mapping and site-specific glycan maturation in vivo

Summary: Glycoprotein processing along a complex highly compartmentalized pathway is a hallmark of eukaryotic cells. We followed the kinetics of intracellular, site-specific glycan processing of a model protein with five distinct N-glycosylation sites and deduced a mathematical model of the secretor...

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Main Authors: Marie-Estelle Losfeld, Ernesto Scibona, Chia-wei Lin, Markus Aebi
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222016893
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author Marie-Estelle Losfeld
Ernesto Scibona
Chia-wei Lin
Markus Aebi
author_facet Marie-Estelle Losfeld
Ernesto Scibona
Chia-wei Lin
Markus Aebi
author_sort Marie-Estelle Losfeld
collection DOAJ
description Summary: Glycoprotein processing along a complex highly compartmentalized pathway is a hallmark of eukaryotic cells. We followed the kinetics of intracellular, site-specific glycan processing of a model protein with five distinct N-glycosylation sites and deduced a mathematical model of the secretory pathway that describes a complex set of processing reactions localized in defined intracellular compartments such as the endoplasmic reticulum the Golgi, or the lysosome. The model was able to accommodate site-specific N-glycan processing and we identified phosphorylated glycan structures of the mannose-6-phosphate pathway responsible for the lysosomal sorting of the glycoprotein. Importantly, our model protein can take different routes of the cellular secretory pathway, resulting in an increased glycan complexity of the secreted protein.
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spelling doaj.art-88ba732ce9b345d58c74d83cbcaf2c2e2022-12-22T04:38:04ZengElsevieriScience2589-00422022-11-012511105417Glycosylation network mapping and site-specific glycan maturation in vivoMarie-Estelle Losfeld0Ernesto Scibona1Chia-wei Lin2Markus Aebi3Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, SwitzerlandInstitute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, SwitzerlandInstitute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, Switzerland; Functional Genomic Center Zürich, CH8057 Zürich, SwitzerlandInstitute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, Switzerland; Corresponding authorSummary: Glycoprotein processing along a complex highly compartmentalized pathway is a hallmark of eukaryotic cells. We followed the kinetics of intracellular, site-specific glycan processing of a model protein with five distinct N-glycosylation sites and deduced a mathematical model of the secretory pathway that describes a complex set of processing reactions localized in defined intracellular compartments such as the endoplasmic reticulum the Golgi, or the lysosome. The model was able to accommodate site-specific N-glycan processing and we identified phosphorylated glycan structures of the mannose-6-phosphate pathway responsible for the lysosomal sorting of the glycoprotein. Importantly, our model protein can take different routes of the cellular secretory pathway, resulting in an increased glycan complexity of the secreted protein.http://www.sciencedirect.com/science/article/pii/S2589004222016893Cell biologyIntegrative aspects of cell biologyMathematical biosciences
spellingShingle Marie-Estelle Losfeld
Ernesto Scibona
Chia-wei Lin
Markus Aebi
Glycosylation network mapping and site-specific glycan maturation in vivo
iScience
Cell biology
Integrative aspects of cell biology
Mathematical biosciences
title Glycosylation network mapping and site-specific glycan maturation in vivo
title_full Glycosylation network mapping and site-specific glycan maturation in vivo
title_fullStr Glycosylation network mapping and site-specific glycan maturation in vivo
title_full_unstemmed Glycosylation network mapping and site-specific glycan maturation in vivo
title_short Glycosylation network mapping and site-specific glycan maturation in vivo
title_sort glycosylation network mapping and site specific glycan maturation in vivo
topic Cell biology
Integrative aspects of cell biology
Mathematical biosciences
url http://www.sciencedirect.com/science/article/pii/S2589004222016893
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AT ernestoscibona glycosylationnetworkmappingandsitespecificglycanmaturationinvivo
AT chiaweilin glycosylationnetworkmappingandsitespecificglycanmaturationinvivo
AT markusaebi glycosylationnetworkmappingandsitespecificglycanmaturationinvivo