Fellgett, Simon W., Maguire, Richard J. and Pownall, Mary Elizabeth orcid.org/0000-0003-2329-5844 (2015) Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling. Journal of Cell Science. pp. 1408-1421. ISSN 0021-9533
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015. Published by The Company of Biologists Ltd . This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Morphogen,Development,Cell signalling,Pronephros,6-O-endosulfatase,Heparan sulfate,HSPG,Wnt |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 21 Jul 2015 12:01 |
Last Modified: | 07 Feb 2025 00:11 |
Published Version: | https://doi.org/10.1242/jcs.164467 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1242/jcs.164467 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88359 |
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Description: Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling