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.
The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Paul F
PF
Langton
Hakuhodo Medical Inc., 6-1-20 Akasaka Minato-ku, Tokyo 107-0052, Japan.
Satoshi
S
Kakugawa
The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London NW7 1AA, UK. Electronic address: JP.Vincent@crick.ac.uk.
Jean-Paul
JP
Vincent
D000818:Animals; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D060449:Wnt Signaling Pathway
D005229:Fatty Acids, Monounsaturated; D051153:Wnt Proteins; C008757:palmitoleic acid