SP2

Principal Investigator: Rüdiger Horstkorte & Astrid Gesper & Kaya Bork (Institute for Physiological Chemistry, MLU Halle-Wittenberg) & Heidi Olzscha (Medical School Hamburg)

Carolin Neu (PhD): The impact of glycosylation and glycation on the generation and uptake of vehicles in aging cells

Tom Schneider (MD): Investigation of the influence of posttranslational modifications such as sialylation and glycation on protein half-life, cell adhesion and migration in wt and GNE-deficient HEK-293 cells

 (Poly)sialylation is integral to numerous cellular processes, including the regulation of cell-cell interactions and protein stability. The key enzyme of the sialic acid biosynthesis pathway is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), which catalyzes the epimerization and subsequent phosphorylation of UDP‑GlcNAc to ManNAc-6-phosphate. In this study, we will use HEK-293 cells and a variant lacking the GNE enzyme to examine how variations in sialylation levels affect the stability of downstream enzymes of the sialic acid biosynthesis pathway—NANS, NANP, and CMAS—as well as proteins that are typically polysialylated. Since a previous ProMoAge project demonstrated the influence of glycation on GNE activity, this study also aims to investigate the interplay between sialylation and glycation and their combined influence on the half-life of the aforementioned enzymes. Additionally, we will explore changes in cell behavior, particularly adhesion and migration, after glycation in these cells. The aim of this study is to elucidate the complex relationships between sialylation, glycation, and protein stability, together with their implications on cellular dynamics.