title: Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling.
abstract: Wnt signalling plays essential roles during embryonic development and is known to be mis-regulated in human disease. There are many molecular mechanisms that ensure tight regulation of Wnt activity. One such regulator is the heparan-sulfate-specific 6-O-endosulfatase Sulf1. Sulf1 acts extracellularly to modify the structure of heparan sulfate chains to affect the bio-availability of Wnt ligands. Sulf1 could, therefore, influence the formation of Wnt signalling complexes to modulate the activation of both canonical and non-canonical pathways. In this study, we use well-established assays in Xenopus to investigate the ability of Sulf1 to modify canonical and non-canonical Wnt signalling. In addition, we model the ability of Sulf1 to influence morphogen gradients using fluorescently tagged Wnt ligands in ectodermal explants. We show that Sulf1 overexpression has ligand-specific effects on Wnt signalling: it affects membrane accumulation and extracellular levels of tagged Wnt8a and Wnt11b ligands differently, and inhibits the activity of canonical Wnt8a but enhances the activity of non-canonical Wnt11b.
authors: Biology Department, University of York, York YO10 5YW, UK.
authors: Simon W
authors: SW
authors: Fellgett
authors: Biology Department, University of York, York YO10 5YW, UK.
authors: Richard J
authors: RJ
authors: Maguire
authors: Biology Department, University of York, York YO10 5YW, UK betsy.pownall@york.ac.uk.
authors: Mary Elizabeth
authors: ME
authors: Pownall
mesh_terms: D000818:Animals; D008024:Ligands; D015398:Signal Transduction; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D051153:Wnt Proteins; D060509:Wnt3A Protein; C555512:Wnt3a protein, zebrafish; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C512785:wnt11b protein, Xenopus; C495248:wnt8a protein, Xenopus; C582441:Sulf1 protein, zebrafish; D013429:Sulfatases
keywords: 6-O-endosulfatase; Cell signalling; Development; HSPG; Heparan sulfate; Morphogen; Pronephros; Wnt