Roles of lipids in transport of Wnt proteins
Abstract: Wnt proteins harbor lipid modifications that profoundly influence their trafficking and function. For instance, Wnt proteins are palmitoylated at serine around amino acids 205-215 by the membrane-bound O-acyltransferase Porcupine in the ER. We could show that in Porcupine knockout cells not all palmitoylation of Wnt was abolished, whereas complete inhibition of fatty acid synthesis led to downregulation of Wnt protein levels, suggesting that the stability of Wnts depend on other enzymes. This project aims to i) to identify lipid modifications of Wnts, ii) to study the contribution of specific lipid modifications to the interactions with other proteins, and iii) to study the roles of different lipids in the stabilization and secretion of the Wnt ligands.