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Modelling glycan processing reveals Golgi-enzyme homeostasis upon trafficking defects and cellular differentiation

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JournalCell reports
DateAccepted/In press - 27 Mar 2019
DatePublished (current) - 23 Apr 2019
Issue number4
Volume27
Pages (from-to)1231-1243.e6
Original languageEnglish

Abstract

The decoration of proteins by carbohydrates is essential for eukaryotic life, yet heterogeneous due to lacking biosynthetic templates. This complex carbohydrate mixture – the glycan profile – is generated in the compartmentalised Golgi, where level and localization of glycosylation enzymes are key determinants. Here we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles. We combined stochastic modelling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters. This is an important development in the field of glycan modelling, which revealed biological insights about the glycosylation machinery in altered cellular states. We experimentally validated changes in Nlinked glycan-modifying enzymes in cells with perturbed intra-Golgi enzyme sorting and the predicted glycan-branching activity during osteogenesis. Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation related diseases and glycan-engineering of cells

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© 2019 The Authors.

    Research areas

  • COG complex, glycan processing, Golgi apparatus, Markov chain Monte Carlo, mass spectrometry, MSCs

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