Making, Exporting, and Modulating Wnts

Wnt proteins activate a conserved signalling pathway that controls development and tissue homeostasis in all metazoans. The intensity of Wnt signalling must be tightly controlled to avoid diseases caused by excess or ectopic signalling. Over the years, many proteins dedicated to Wnt function have been identified, including Porcupine, which appends a palmitoleate moiety that is essential for signalling activity. This lipid inevitably affects subcellular trafficking and solubility, as well as providing a target for post-translational modulation. We review here the life history of Wnts, starting with progression through the secretory pathway, continuing with release and spread in the extracellular space, and finishing with the various proteins that dampen or inactivate Wnts in the extracellular space.