title: Extracellular modulators of Wnt signalling.
abstract: Wnt morphogens are secreted signalling proteins that play leading roles in embryogenesis and tissue homeostasis throughout life. Wnt signalling is controlled by multiple mechanisms, including posttranslational modification of Wnts, antagonist binding (to Wnts or their receptors), and regulation of the availability of Wnt receptors. Recent crystallographic, structure-guided biophysical and cell-based studies have advanced our understanding of how Wnt signalling is regulated at the cell surface. Structures include Wnt in complex with the cysteine-rich domain (CRD) of Frizzled, extracellular fragments of Wnt co-receptor LRP6, LRP6-binding antagonists Dickkopf and Sclerostin, antagonists 5T4/WAIF1 and Wnt inhibitory factor 1 (WIF-1), as well as Frizzled-ubiquitin ligases ZNRF3/RNF43 (in isolation and in complexes with Wnt signalling promoters R-spondins and LGR5). We review recent discoveries and remaining questions.
authors.affiliation: Cold Spring Harbor Laboratory, W. M. Keck Structural Biology Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Malinauskas
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom. Electronic address: yvonne@strubi.ox.ac.uk.
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
mesh_terms: D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D051157:Frizzled Receptors / Q000737:chemistry; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000737:chemistry; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry; D051153:Wnt Proteins / Q000737:chemistry; D060449:Wnt Signaling Pathway
chemical_list: D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D051157:Frizzled Receptors; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051153:Wnt Proteins; D044767:Ubiquitin-Protein Ligases; D003545:Cysteine