title: 'Glyco-deglyco' processes during the synthesis of N-glycoproteins.
abstract: 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 Man5GlcNAc2-PP-Dol. The Man5GlcNAc2-P, as the main product, is recovered in the cytosolic compartment and is further degraded to Man5GlcNAc1 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 alpha-glucosidases and rough ER mannosidase and are (mainly as Man8GlcNAc2) exported into the cytosolic compartment. This material is further degraded into a single component, the Man5GlcNAc1: Man alpha 1-2Man alpha 1-2Man alpha 1-3 (Man alpha 1-6)Man beta 1-4GlcNAc 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.
authors.affiliation: Laboratoire de Chimie Biologique, UMR 111 du CNRS/USTL, Université des Sciences et Technologies de Lille, France.
authors.forename: R
authors.initials: R
authors.lastname: Cacan
authors.forename: S
authors.initials: S
authors.lastname: Duvet
authors.forename: D
authors.initials: D
authors.lastname: Kmiécik
authors.forename: O
authors.initials: O
authors.lastname: Labiau
authors.forename: A M
authors.initials: AM
authors.lastname: Mir
authors.forename: A
authors.initials: A
authors.lastname: Verbert
mesh_terms: D000818:Animals; D005964:Glucosyltransferases / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D009844:Oligosaccharides / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D009844:Oligosaccharides; C028569:oligomannoside; D005964:Glucosyltransferases; C054676:dolichol phosphate glucose-dolichol diphosphate oligosaccharide glucosyltransferase