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J Cell Sci 2015 Apr 01;1287:1408-21. doi: 10.1242/jcs.164467.
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Sulf1 has ligand-dependent effects on canonical and non-canonical Wnt signalling.

Fellgett SW , Maguire RJ , Pownall ME .

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.

PubMed ID: 25681501
PMC ID: PMC4379729
Article link: J Cell Sci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: atf2 chrd dvl2 fzd8 mmut mt-tr myc nodal3.1 odc1 sulf1 trna wnt11 wnt11b wnt3a wnt8a
Antibodies: HA Ab3 Myc Ab7

Article Images: [+] show captions
References [+] :
Ai, QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. 2003, Pubmed