Free N-linked oligosaccharide chains: Formation and degradation

There is growing evidence that N-linked glycans play pivotal roles in protein folding and intra- and/or intercellular trafficking of N-glycosylated proteins. It has been shown that during the N-glycosylation of proteins, significant amounts of free oligosaccharides (free OSs) are generated in the lumen of the endoplasmic reticulum (ER) by a mechanism which remains to be clarified. Free OSs are also formed in the cytosol by enzymatic deglycosylation of misfolded glycoproteins, which are subjected to destruction by a cellular system called “ER-associated degradation (ERAD).” While the precise functions of free OSs remain obscure, biochemical studies have revealed that a novel cellular process enables them to be catabolized in a specialized manner, that involves pumping free OSs in the lumen of the ER into the cytosol where further processing occurs. This process is followed by entry into the lysosomes. In this review we summarize current knowledge about the formation, processing and degradation of free OSs in eukaryotes and also discuss the potential biological significance of this pathway. Other evidence for the occurrence of free OSs in various cellular processes is also presented.