A novel lectin in the secretory pathway

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Abstract
How important can sugars be? Sure, glycoproteins need their glycans during synthesis for proper folding: the sugar chain increases solubility and prevents aggregation, and it mediates interactions with various proteins. On the other hand, so many different glycans exist on glycoproteins that it is difficult to imagine that each would have a specific function. Still, now and again, a new protein is identified that interacts with a particular carbohydrate chain, and that turns out to be crucial for a particular stage in the biosynthesis and maturation of glycoproteins. Will there be many, or do we have only a few? Whichever the answer, glycobiology is celebrating a certain revival. The first step of N‐linked glycosylation is highly conserved amongst eukaryotic organisms: the Glc3Man9GlcNAc2 glycan chain is co‐translationally attached to the Asn residue in the consensus motif Asn‐X‐Ser/Thr (Kornfeld and Kornfeld, 1985). Immediately after attachment, monosaccharides are removed one by one (Figure 1), only to prepare the glycan for the later addition of other monosaccharides. This apparently futile sequence of events is a consequence of the necessary signaling to glycan‐specific lectins with various gate‐keeper functions in the secretory pathway (Helenius and Aebi, 2001). Figure 1. Modifications of the N‐linked glycan on proteins. Glycans are attached as the high mannose Glc3Man9GlcNAc2 chain. Immediately after attachment to the protein, the first glucose residue (triangle) is removed by glucosidase I, the second and third by glucosidase II. The third glucose can be reattached by a glucosyltranferase that recognizes only misfolded and unfolded proteins (Parodi, 2000; Helenius and Aebi, 2001). Calnexin and its soluble family member calreticulin (not depicted) associate with the monoglucose chain to retain immature glycoproteins in the ER, to allow folding to proceed, and to prevent release into the …