Glycosylation network mapping and site-specific glycan maturation in vivo

Marie-Estelle Losfeld; Ernesto Scibona; Chia-Wei Lin; Markus Aebi

doi:10.1016/j.isci.2022.105417

Glycosylation network mapping and site-specific glycan maturation in vivo

iScience. 2022 Oct 20;25(11):105417. doi: 10.1016/j.isci.2022.105417. eCollection 2022 Nov 18.

Authors

Marie-Estelle Losfeld¹, Ernesto Scibona², Chia-Wei Lin^{1

3}, Markus Aebi¹

Affiliations

¹ Institute of Microbiology, Department of Biology, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, Switzerland.
² Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, CH8093 Zürich, Switzerland.
³ Functional Genomic Center Zürich, CH8057 Zürich, Switzerland.

Abstract

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.

Keywords: Cell biology; Integrative aspects of cell biology; Mathematical biosciences.