["Glyco-deglyco" processes during the biosynthesis of glycoproteins]

For the past fifteen 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-glucosylated 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 not-yet 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 (rough ER). They are further submitted to processing a-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, by the sequential action of a cytosolic neutral chitobiase followed by cytosolic mannosidase(s). Furthermore, OS-Gn1 could have a dual origin: in 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 remodelling 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 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. This review is dedicated to Pr Paul Boulanger who has spent a large part of his career to determine the structure of proteins in order to understand their functions. If it is well established that many biological functions are born by proteins, it appears more and more evident that co- or post translational modifications are of importance in the modulation of these functions. Among them, the glycosylation appears as a major event which intervene in the 3D structure of the protein, which control his biological time-life and which may act in many recognition processes.