## 1 Protein Glycoslation and the Golgi  
The enzymatic addition of glycans to proteins, dubbed \"protein glycosylation\", is a fundamental post-translation and co-translational modification that controls the folding and stability of proteins and their transport through the secretory pathway [1; 2; 3]. The composite repertoire of glycan structures in glycoproteins impacts on many different cellular and developmental processes such as signal transduction, molecular trafficking, cell-cell communication, immunity and early mammalian development [4; 5]. Since one fifth of all proteins in structural databases are classified as glycoproteins, it is not surprising that up to 2% of the eukaryotic proteome is required for glycosylation [3; 6]. It has been estimated that 700 proteins are required to generate the glycan structures in human glycome [7]. Glycoprotein glycosylation is a sequential process that involves the coordinated action of hundreds of glycosyltransferases (GTs) and glycosylases, which are trafficked to the specific locations of the endoplasmic reticulum (ER) and Golgi apparatus [8]. Only ten monosaccharides are essential for the synthesis of animal glycans: glucose (Glc), galactose (Gal), \(N\)-acetylglglucosamine (GlcNAc), \(N\)-acetylglalactosamine (GalNAc), fucose (Fuc), mannose (Man), xylose (Xyl), glucuronic acid (GlcA), sialic acid (SA, either as \(N\)-acetylneuraminic acid, Neu5 Ac or 5-\(N\)-glycolyneuraminic acid acid, Neu5 Gc). The main types of protein glycoprotein glycans are \(N\)- or \(O\)-linked. \(N\)-glycosylation starts in the ER with the synthesis of a glycan precursor with the composition Glc3 Man9 GlcNa2 on the carrier dolichol isopenoid lipid [9]. The precursor glycan is then transferred en bloc onto asparagine residues of nascent proteins by multisubunit oligosaccharidesyltransferase (OST) complexes within the lumen of the ER [10; 11; 12]. Distal glucose moieties of the Glc3 Man9 GlcNac2 glycan are trimmed before reaching the Golgi apparatus by sequential actions of ER glucosidases, representing an important step in the control of folding processes for secretory pathway glycoproteins prior to ER exit [13; 14; 15]. Glycoprotein that exit the ER reach the Golgi apparatus with eight or nine mannose residues for further processing of the glycan moieties into complex and hybrid glycan forms (Figure 1). The Golgi apparatus is organized into discrete cisternae, each containing a distinct subset of glycosylation machinery proteins which include glycosyltransferases, glycosidases and nucleotide sugar transporters [16; 17]. As the secretory proteins arrive at the _cis_-Golgi, mannose trimming generates the Man5 GlcNAcNAc2 Asn intermediate followed by the transfer of GlcNAc residue to a terminal Man residue on the \(\alpha\)3-arm of the glycan structure by the medial Golgi GT GlcNAcT-1. The addition of GlcNAc to Man5 GlcNAc2 Asn is an essential step to generate hybrid and complex \(N\)-linked glycans [15; 17]. Hybrid \(N\)-glycans are generated by the extension of the \(\alpha\)3-arm that received GlcNAc with the addition of Gal, GalNAc, Fuc and SA. Removal of two terminal of the five Man residues, allows branching with an additional GlcNAc residue and synthesis of biantennary complex \(N\)-glycans. Further branching may occur, leading to multiantennary complex glycans in _medial-late_ and _trans_-Golgi compartments [17; 18]. Complex glycans can be decorated with Gal, GalNAc, Fuc and SA. In contrast to \(N\)-linked glycosylation, \(O\)-glycosylation does not involve a lipid-linked oligosaccharidescharide precursor for transfer to nascent polypeptides. Instead, it consists of the formation of a single glycosidic linkage between Ser or Thr residues and GalNAc, Man, Glc, Xyl, or Fuc [17]. The most abundant type of \(O\)-glycans are the mucins initiated by GalNAc-Ser/Thr and the glycosaminoglycan (GAG) chains on proteoglycans initiated by a conserved tetrasaccharide Glc-A-\(\beta\)1,3-Gal-\(\beta\)1.3-Gal-\(\beta\)1,4 Xyl-\(\beta\) (Figure 1).