Abstract
The Golgi is the central organelle of the secretory pathway and it houses the majority of the glycosylation machinery, which includes glycosylation enzymes and sugar transporters. Correct compartmentalization of the glycosylation machinery is achieved by retrograde vesicular trafficking as the secretory cargo moves forward by cisternal maturation. The vesicular trafficking machinery which includes vesicular coats, small GTPases, tethers and SNAREs, play a major role in coordinating the Golgi trafficking thereby achieving Golgi homeostasis. Glycosylation is a template-independent process, so its fidelity heavily relies on appropriate localization of the glycosylation machinery and Golgi homeostasis. Mutations in the glycosylation enzymes, sugar transporters, Golgi ion channels and several vesicle tethering factors cause congenital disorders of glycosylation (CDG) which encompass a group of multisystem disorders with varying severities. Here, we focus on the Golgi vesicle tethering and fusion machinery, namely, multisubunit tethering complexes and SNAREs and their role in Golgi trafficking and glycosylation. This review is a comprehensive summary of all the identified CDG causing mutations of the Golgi trafficking machinery in humans.
Highlights
Eukaryotic cells have a remarkable feature of intracellular compartments or organelles enclosed by lipid membranes
A case study of a 6-year-old patient carrying a mutation in VPS51 showed abnormal glycosylation testing, and her phenotype had substantial similarity with that seen in congenital disorders of glycosylation (CDG)
This study demonstrated that this defect in Golgi enzymes only occurs in Golgi-Associated Retrograde Protein Complex (GARP)-deficient cells and not in endosome associated recycling protein (EARP)-deficient cells
Summary
Eukaryotic cells have a remarkable feature of intracellular compartments or organelles enclosed by lipid membranes. The currently accepted cisternal maturation model of Golgi transport describes that the anterograde cargo stays in the Golgi cisternae and is carried forward by the gradual maturation of the cis-Golgi to the trans-Golgi while Golgi resident proteins are cycled back to newly formed cisternae [3,4,5,6]. This way, the identity of each compartment is maintained even as the cisternal maturation goes on. Lipids and proteins transported by the secretory pathway undergo modifications such as glycosylation within the Golgi. Glycan mass spectrometry and/or ApoCIII IEF are often used to complement transferrin IEF testing [17]
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