Ludger Johannes
Institut Curie, Paris
GlycoSwitch — a novel signaling circuit to control endocytosis
It is commonly assumed that the glycan makeup of glycoproteins is final and static once these have reached the cell surface. Here, we challenge this notion by the discovery of a molecular switch — termed GlycoSwitch — that at the plasma membrane induces acute and reversible changes of glycan structure and arrangement in space [1,2]. This leads to the binding and oligomerization of galectins that in interaction with glycosphingolipids drive the formation of tubular endocytic pits from which clathrin-independent endocytic carriers emerge for uptake and retrograde trafficking of the glycoproteins to the Golgi apparatus. Here, the glycoproteins are resialylated and secreted in a polarized manner to specialized areas of the cells, such as the leading edge in migrating cells. We are now exploring the structural, molecular, and pathophysiological aspects of the GlycoSwitch, notably in polarized trafficking across intestinal enterocytes and in epithelial-mesenchymal plasticity in breast cancer.
Selected references
1. MacDonald E, (…), and Johannes L. Growth factor-triggered desialylation controls glycolipid-lectin driven endocytosis. Nat Cell Biol 27: 449-463, 2025.
2. Shafaq-Zadah M, (…), and Johannes L. Spatial N-glycan rearrangement on a5b1 integrin nucleates galectin-3 oligomers to determine endocytic fate. Nat Commun 16: 9461, 2025.