Glypicans shield the Wnt lipid moiety to enable signalling at a distanceMore about Open Access at the Crick
Authors listIan Mcgough Luca Vecchia Benjamin Bishop Tomas Malinauskas Karen Beckett Dhira Joshi Nicola O'Reilly Christian Siebold E Yvonne Jones Jean-Paul Vincent
A relatively small number of proteins have been suggested to act as morphogens-signalling molecules that spread within tissues to organize tissue repair and the specification of cell fate during development. Among them are Wnt proteins, which carry a palmitoleate moiety that is essential for signalling activity. How a hydrophobic lipoprotein can spread in the aqueous extracellular space is unknown. Several mechanisms, such as those involving lipoprotein particles, exosomes or a specific chaperone, have been proposed to overcome this so-called Wnt solubility problem. Here we provide evidence against these models and show that the Wnt lipid is shielded by the core domain of a subclass of glypicans defined by the Dally-like protein (Dlp). Structural analysis shows that, in the presence of palmitoleoylated peptides, these glypicans change conformation to create a hydrophobic space. Thus, glypicans of the Dlp family protect the lipid of Wnt proteins from the aqueous environment and serve as a reservoir from which Wnt proteins can be handed over to signalling receptors.
Issue number 7823
Full text links
Publisher website (DOI) 10.1038/s41586-020-2498-z
Europe PubMed Central 32699409