Growth factor induced desialylation for the fast control of endocytosis

It is commonly assumed that the glycan makeup of glycoproteins is final and static once these have reached the cell surface. Here, we discovered a molecular switch involving acute changes of glycans at the plasma membrane that challenges this notion. We demonstrate that growth factors tune within minutes the endocytosis of cell surface glycoproteins through a unique mechanism of pH-triggered enzymatic removal of sialic acids. The subsequent retrograde transport of these desialylated glycoproteins to the Golgi apparatus allows for the resetting of their glycan makeup and the repurposing of their functions through polarized re-secretion to specialized plasma membrane areas, such as the leading edge to sustain cell motility. Thus, glycosylation thereby emerges as a dynamic regulatory post-translational modification similar to phosphorylation and ubiquitylation.