‘Glyco-deglyco’ processes during the synthesis of N-glycoproteins

• Published in: Biochimie 1998, Vol.80 (1), p.59-68
• Main Authors: Cacan, R., Duvet, S., Kmiécik, D., Labiau, O., Mir, A.M., Verbert, A.
• Format: Article
• Language: English
• Subjects: Animals; endoplasmic reticulum; Glucosyltransferases - metabolism; Glycoproteins - biosynthesis; Glycosylation; Humans; lipid intermediates; Models, Biological; N-glycosylation; oligomannoside trafficking; Oligosaccharides - metabolism
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/S0300-9084(98)80057-6

For the past 15 years, it has appeared increasingly evident that the N-glycosylation process was accompanied by the release of oligomannoside type oligosaccharides. This material is constituted of oligosaccharide-phosphates and of neutral oligosaccharides possessing one GlcNAc (OS-Gn1) or two GlcNAc (OS-Gn2) at the reducing end. It has been demonstrated that oligosaccharide-phosphates originated from the cleavage by a specific pyrophosphatase, of non-glycosylated cytosolic faced oligosaccharide-PP-Dol and chiefly the Man 5GlcNAc 2-PP-Dol. The Man 5GlcNAc 2-P, as the main product, is recovered in the cytosolic compartment and is further degraded to Man 5GlcNAc 1 by as for yet not depicted enzymes. In contrast, OS-Gn2 produced from hydrolysis of oligosaccharide-PP-Dol (presumably as a transfer reaction onto water) when the amount of protein acceptor is limiting, are generated into the lumen of rough endoplasmic reticulum (ER). They are further submitted to processing α-glucosidases and rough ER mannosidase and are (mainly as Man 8GlcNAc 2) exported into the cytosolic compartment. This material is further degraded into a single compartment, the Man 5GlcNAc 1: Manα1-2Manα1-2Manα1–3 (Manα1–6)Manβ1-4GlcNAc by the sequential action of a cytosolic neutral chitobiase followed by cytosolic mannosidase. Furthermore, OS-Gn1 could have a dual origin: on the one hand, they originate from OS-Gn2 by the cytosolic degradation pathway indicated above: on the other hand, we will discuss a possible origin from the degradation or remodeling of newly synthesized glycoproteins. Considered first as a minor phenomenon, these observations have lead to the concept of intracellular oligomannoside trafficking, a process which results from more fundamental phenomena such as the control of the dolichol cycle, and the so-called quality-control of glycoprotein. In this review, we would like to describe the evolution of ideas on the origin, intracellular trafficking and putative roles of these oligomannosides released during the N-glycosylation process. We propose that these early stage ‘glyco-deglyco’ processes represent a way of control of N-glycosylation and of the fate of N-glycoproteins.