Free oligomannosides produced during the N-glycosylation process: Origin, intracellular trafficking and putative roles

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-Gn(1)) or two GlcNAc (OS-Gn(2)) 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 Man(5)GlcNAc(2)-PP-Dol. The Man(5)GlcNAc(2)-P, as the main product, is recovered in the cytosolic compartment and is further degraded to Man(5)GlcNAc(1) by not-yet depicted enzymes. In contrast, OS-Gn(2) 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 Man(8)GlcNAc(2)) exported into the cytosolic compartment. This material is further degraded into a single component, the Man(5)GlcNAc(1): Man alpha 1-->2 Man 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-Gn(1) could have a dual origin : in one hand, they originate from OS-Gn(2) by the cytosolic degradation pathway indicated above, on the other hand, we will discuss a possible origin from the degradation 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 glycoproteins. 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.