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Title: Genetics of Golgi apparatus regulation in mammalian cells
Keywords: Golgi, glycosylation, ERK8, Cancer, membrane trafficking
Issue Date: 6-Dec-2013
Source: CHIA ZHIHUI JOANNE (2013-12-06). Genetics of Golgi apparatus regulation in mammalian cells. ScholarBank@NUS Repository.
Abstract: Protein glycosylation modifies many different proteins and depends intimately on the compartmentalized organization of the Golgi apparatus. An image-based RNAi screen against kinases and phosphatases identified 159 genes whose depletion strongly affected Golgi morphology. Most gene depletion also affected glycan biosynthesis, suggesting that signaling cascades control glycosylation through Golgi remodeling. We focused on O-glycosylation initiation regulation and we found it to be controlled through trafficking of glycosyltransferases GalNAc-Ts from the Golgi to ER. The atypical MAPK ERK8 is a potent regulator of this trafficking through inhibition of COPI transport carriers formation. We also find that ERK8 is a negative regulator of cell motility and that this effect is strictly dependent on O-glycosylation. These results appear to be highly significant for human health as ER-localized O-glycosylation is frequently upregulated in human tumors, while ERK8 expression is frequently lost, suggesting a novel mechanism for the acquisition of invasiveness.
Appears in Collections:Ph.D Theses (Open)

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