Abstract
Glycosylation is an important post-translational modification for both intracellular and secreted proteins. For glycosylation to occur, cargo must be transported after synthesis through the different compartments of the Golgi apparatus where distinct monosaccharides are sequentially bound and trimmed, resulting in increasingly complex branched glycan structures. Of utmost importance for this process is the intraorganellar environment of the Golgi. Each Golgi compartment has a distinct pH, which is maintained by the vacuolar H+-ATPase (V-ATPase). Moreover, tethering factors such as Golgins and the conserved oligomeric Golgi (COG) complex, in concert with coatomer (COPI) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion, efficiently deliver glycosylation enzymes to the right Golgi compartment. Together, these factors maintain intra-Golgi trafficking of proteins involved in glycosylation and thereby enable proper glycosylation. However, pathogenic mutations in these factors can cause defective glycosylation and lead to diseases with a wide variety of symptoms such as liver dysfunction and skin and bone disorders. Collectively, this group of disorders is known as congenital disorders of glycosylation (CDG). Recent technological advances have enabled the robust identification of novel CDGs related to membrane trafficking components. In this review, we highlight differences and similarities between membrane trafficking-related CDGs.
Highlights
The conjugation of oligosaccharide structures to proteins, glycosylation, is a ubiquitous and fundamental post-translational modification found in all domains of life
Synthesized glycoproteins emanating from the ER enter the Golgi apparatus at the cis-Golgi, sequentially pass through medial- and trans-Golgi, and exit the Golgi at the trans-Golgi network (TGN)
After Golgins mediate the capture of Golgi-destined vesicles from the cytosol, the conserved oligomeric Golgi (COG) complex functions as a tether to anchor COPI vesicles to the Golgi membrane [137,138,139]
Summary
The conjugation of oligosaccharide structures to proteins, glycosylation, is a ubiquitous and fundamental post-translational modification found in all domains of life. The organization of Golgi-resident enzymes and the Golgi apparatus itself differs between cell types, contributing to glycoprotein diversity [28,36,37,38,39]. An important factor involved in the correct trafficking of glycosylation enzymes is the maintenance of pH within the Golgi apparatus. The diversity in V0a subunits is likely important for specific cell type-dependent functions and differential regulation of the pH in different organelles. Given the pH optima of glycosylation enzymes, this pH gradient could restrict the activity of glycosylation enzymes to their target Golgi compartment [52] This might not be the complete explanation considering the broad distribution of pH optima and the small differences in absolute pH between the cisternae. This review serves to provide a comprehensive overview of trafficking-related CDGs and to form a detailed understanding of how Golgi trafficking influences glycosylation
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