Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling
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 extracellularl...
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| Veröffentlicht in: | Journal of cell science 2015-04, Vol.128 (7), p.1408-1421 |
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| creator | Fellgett, Simon W Maguire, Richard J Pownall, Mary Elizabeth |
| description | 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. |
| doi_str_mv | 10.1242/jcs.164467 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9533</identifier><identifier>EISSN: 1477-9137</identifier><identifier>DOI: 10.1242/jcs.164467</identifier><identifier>PMID: 25681501</identifier><language>eng</language><publisher>England: The Company of Biologists</publisher><subject>Animals ; Ligands ; Signal Transduction ; Sulfatases - genetics ; Sulfatases - metabolism ; Wnt Proteins - genetics ; Wnt Proteins - metabolism ; Wnt3A Protein - genetics ; Wnt3A Protein - metabolism ; Xenopus laevis - embryology ; Xenopus laevis - genetics ; Xenopus laevis - metabolism ; Xenopus Proteins - genetics ; Xenopus Proteins - metabolism ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>Journal of cell science, 2015-04, Vol.128 (7), p.1408-1421</ispartof><rights>2015. 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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.</description><subject>Animals</subject><subject>Ligands</subject><subject>Signal Transduction</subject><subject>Sulfatases - genetics</subject><subject>Sulfatases - metabolism</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt3A Protein - genetics</subject><subject>Wnt3A Protein - metabolism</subject><subject>Xenopus laevis - embryology</subject><subject>Xenopus laevis - genetics</subject><subject>Xenopus laevis - metabolism</subject><subject>Xenopus Proteins - genetics</subject><subject>Xenopus Proteins - metabolism</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>0021-9533</issn><issn>1477-9137</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdtKAzEQhoMotlZvfADZSxG2ZnLY7N4IUjxBQUHFy5BmJ-2WNFs3reDbG2mtejWnj3-G-Qk5BToEJtjl3MYhFEIUao_0QSiVV8DVPulTyiCvJOc9chTjnFKqWKUOSY_JogRJoU-entfeQTYzMfPN1IQ6r3GJocawytA5tKuYtSGzJrShscZnCclSnv923hIam2kw3jdhekwOnPERT7ZxQF5vb15G9_n48e5hdD3OLVflKucMa1kUslJYO8nSJucMCm6hrEqGgBNRAgjJ1SRlJZOpKpkB50oFKBwfkKuN7nI9WWBt08Gd8XrZNQvTferWNPr_JDQzPW0_tOCqSm9IAudbga59X2Nc6UUTLXpvArbrqKEoKiEZFzShFxvUdm2MHbrdGqD62wKdLNAbCxJ89vewHfrzc_4FOMuCxQ</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Fellgett, Simon W</creator><creator>Maguire, Richard J</creator><creator>Pownall, Mary Elizabeth</creator><general>The Company of Biologists</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><title>Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling</title><author>Fellgett, Simon W ; Maguire, Richard J ; Pownall, Mary Elizabeth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-32ed566597edf52ffeffae43c18982e1eb48114537bb4882581182a1ff871e4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Ligands</topic><topic>Signal Transduction</topic><topic>Sulfatases - genetics</topic><topic>Sulfatases - metabolism</topic><topic>Wnt Proteins - genetics</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt3A Protein - genetics</topic><topic>Wnt3A Protein - metabolism</topic><topic>Xenopus laevis - embryology</topic><topic>Xenopus laevis - genetics</topic><topic>Xenopus laevis - metabolism</topic><topic>Xenopus Proteins - genetics</topic><topic>Xenopus Proteins - metabolism</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fellgett, Simon W</creatorcontrib><creatorcontrib>Maguire, Richard J</creatorcontrib><creatorcontrib>Pownall, Mary Elizabeth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cell science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fellgett, Simon W</au><au>Maguire, Richard J</au><au>Pownall, Mary Elizabeth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling</atitle><jtitle>Journal of cell science</jtitle><addtitle>J Cell Sci</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>128</volume><issue>7</issue><spage>1408</spage><epage>1421</epage><pages>1408-1421</pages><issn>0021-9533</issn><eissn>1477-9137</eissn><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. 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| ispartof | Journal of cell science, 2015-04, Vol.128 (7), p.1408-1421 |
| issn | 0021-9533 1477-9137 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists |
| subjects | Animals Ligands Signal Transduction Sulfatases - genetics Sulfatases - metabolism Wnt Proteins - genetics Wnt Proteins - metabolism Wnt3A Protein - genetics Wnt3A Protein - metabolism Xenopus laevis - embryology Xenopus laevis - genetics Xenopus laevis - metabolism Xenopus Proteins - genetics Xenopus Proteins - metabolism Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling |
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