# Getting Sugar Coating Right! The Role of the Golgi Trafficking Machinery in Glycosylation
###### 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.  
G 2021 19 November 20  
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. The different known types of glycosylation are classified according to the amino acid residue to which the carbohydrate is attached. In humans, N-glycosylation and O-glycosylation are the two main types. N-glycans are where glycans are attached to Asn in the consensus peptide sequence Asn-X-Ser/Thr, while O-glycans are where glycans are attached to hydroxyl groups of serine or threonine. N-glycosylation is a well-defined process that begins in the ER while O-glycosylation is more varied and mostly begins in the Golgi [7; 8; 9; 10]. Protein glycosylation includes the addition of N-linked glycans, O-linked glycans, phosphorylated glycans, glycosamino-glycans and glycosylphosphatidylinositol (GPI) anchors to peptide backbones as well as C-mannosylation of tryptophan residues [11]. The Golgi houses the majority of the glycosylation machinery within its cisternae. The glycosyltransferases, glycosidases together with their accessory machinery, modify and process glycans as they traverse the Golgi. At the TGN, fully processed glycoconjugates are packaged into carrier membranes and transported to appropriate destinations.  
The glycosylation of macromolecules is involved in nearly every biological process and its defects give rise to various pathologies [11; 12]. Glycoslation defects affect multiple organ systems with varying severities, and they fall under the umbrella of congenital disorders of glycosylation (CDG). CDGs are autosomal recessive inherited diseases due to mutations in genes involved in glycosylation [13; 14]. CDGs are further subdivided into type I (CDG-I) and type II (CDG-II) [15; 16]. CDG-I is due to defects in the transfer of preassembled dolichol-glycan in the ER (or cytosol). Defects in glycan processing in the Golgi give rise to CDG-II. Formerly, a CDG diagnosis was made only based on the isoelectric focusing of serum transferrin which only detected N-glycosylation defects. Nowadays, glycan mass spectrometry and/or ApoE1 EF are often used to complement transferrin IEF testing [17].