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.

STX5’s flexibility in SNARE pairing supports Golgi functions

“…Glycosylation is a template-independent process which is entirely dependent on the sequence of enzyme-substrate interactions (D'Souza et al, 2021). Anterograde cargo molecules delivered from the ER, traverse the Golgi by cisternal maturation, and encounter glycosylation enzymes localized in each of the Golgi cisternae.…”

Acute COG inactivation unveiled its immediate impact on Golgi and illuminated the nature of intra-Golgi recycling vesicles

“…Newly synthesized proteins are delivered from the endoplasmic reticulum (ER) to Golgi for processing, sorting, and secretion (Ungar et al ., 2006; I. Pokrovskaya et al ., 2011; Cottam and Ungar, 2012; Willett, Ungar and Lupashin, 2013; Huang and Wang, 2017; D’Souza, Taher and Lupashin, 2020; D’Souza et al ., 2021). Glycosylation is one of the major cargo modifications chiefly carried out by the Golgi (Stanley, 2011).…”

“…During maturation, each Golgi cisterna needs to maintain its specific set of glycosylation enzymes, sugar transporters, and other cargo modifiers. Proper cisternal compartmentalization of the glycosylation machinery is vital as glycosylation is template independent (Berninsone and Hirschberg, 2000; Stanley, 2011; D’Souza, Taher and Lupashin, 2020; D’Souza et al ., 2021). There are continuous discussions on the exact mechanisms and pathways used by different cells and organisms for the anterograde cargo transport through the Golgi (Orci, Ravazzola, et al ., 2000; Pelham, 2001; Hwang, 2008; Mironov and Beznoussenko, 2019), but the majority of recent studies agree on general rules for the maintenance of Golgi enzymes.…”

“…It is reported that both active retention and recycling mechanisms are utilized to maintain the proper localization of Golgi resident proteins (Glick and Nakano, 2009; Rizzo et al ., 2013). The recycling of Golgi resident proteins and enzymes is mostly facilitated by COPI vesicle-mediated retrograde transport (Pelham, 2001; Cottam and Ungar, 2012; Di Martino, Sticco and Luini, 2019; D’Souza et al ., 2021; Park et al ., 2021). A balance between anterograde and retrograde transport is not only important for maintaining proper concentration of the resident Golgi proteins and lipids but also for the cell’s physiology (Blackburn, D’Souza and Lupashin, 2019; D’Souza, Taher and Lupashin, 2020).…”

“…A balance between anterograde and retrograde transport is not only important for maintaining proper concentration of the resident Golgi proteins and lipids but also for the cell’s physiology (Blackburn, D’Souza and Lupashin, 2019; D’Souza, Taher and Lupashin, 2020). The vesicular trafficking machinery consists of several distinct modules that drive vesicle budding from a donor compartment followed by its transport, tethering, and fusion with the acceptor compartment (Cai, Reinisch and Ferro-Novick, 2007; Cottam and Ungar, 2012; D’Souza et al ., 2021). Vesicle formation is initiated by small ARF family GTPases that recruit coat proteins which collect and segregate cargo molecules into 60 mm vesicles.…”