Membrane glycoproteins get another go: the GlycoSwitch

The glycan makeup of membrane glycoproteins and glycosphingolipids at the cell surface is traditionally viewed as mature and static. Recent findings challenge this view, showing that selective glycan remodeling can redirect membrane glycoproteins back to the Golgi for another go. In this review we discuss the glycosylation processes in cells, with a focus on the terminal glycan chains on proteins and lipids that are capped by sialic acid sugars, and that engage the glycan-binding proteins of the galectin family. We highlight new studies demonstrating that growth factors trigger the removal of sialic acid by endogenous neuraminidases at the cell surface, leading to glycolipid-lectin driven endocytosis and retrograde traffic to the Golgi. This molecular circuit, termed the GlycoSwitch, introduces new perspectives on glycan-mediated regulation of cellular functions.