Secretion of Wnt proteins

Secretion of Wnt proteins

Upon translation, Wnt proteins (yellow ovals) undergo a series of modifications as they transit through the secretory pathway and associate with several proteins, including Porcupine (Porc) in the endoplasmic reticulum. All Wnt proteins harbor a covalent lipid modification: a palmitate, attached by the palmitoyltransferase Porcupine. The transmembrane protein Wntless (Wls) exclusively binds to lipidated Wnt proteins and transfers them to the plasma membrane for secretion. Nygaard et al (2020) reported on a 3.2 Å resolution cryo-EM structure of WNT8A bound to Wntless, with a Wnt hairpin inserted into a conserved hydrophobic cavity in the Wntless protein. Once secreted, Wnt proteins may be incorporated into secretory vesicles wherein Wls continues to bind Wnt proteins, perhaps presenting lipidated Wnt proteins to their cognate Frizzled receptors. see for a review: Routledge D, Scholpp, S. Mechanisms of intercellular Wnt transport. Development. 2019 May 15;146(10). pii: dev176073. doi: 10.1242/dev.176073.