Mathematical modeling of protein secretion by monitoring intracellular N-glycan processing
In a joint effort, researchers of the groups of Markus Aebi (IMB), Massimo Morbidelli (D-CHAB) and Merck Healthcare have combined MS-based analytical methods and modeling approaches to describe the processing pathways of recombinant IgG in CHO cells. The paper in Science Advances provides a kinetic description of the secretory pathway in mammalian cells.
Protein secretion in eukaryotes is a highly organized process that involves different cellular organelles (e.g. Endoplasmic Reticulum, Golgi, Lysosome) connected by a vesicular transport system. Along this pathway, glycoproteins are processed by differentially localized glycosyltransferases and glycosylhydrolases. Using a glycoproteomics approach that combines targeted detection of glycopeptides with time-resolved SILAC labeling, the intracellular processing of recombinant IgG in CHO cells was quantified. The glycostructure-specific turnover rates provided the experimental data for a mathematical model of intracellular glycoprotein processing and secretion. The model confirms specific properties of the pathway (e.g localized expression of processing enzymes in the different Golgi cisternae) and proposes novel processes such as the rapid export of aggregated proteins from the ER to the degrading lysosome.
Link to the publication in external pageScience Advances