Secreted Frizzled-related proteins enhance the diffusion of Wnt ligands and expand their signalling range.
Secreted Frizzled-related proteins (sFRPs) are thought to negatively modulate Wnt signalling. Although Wnt proteins are thought to diffuse extracellularly and act as morphogens, little is known about the diffusibility of either Wnts or sFRPs. Here we show that Frzb and Crescent (Cres), which are members of the sFRP family, have the ability to regulate the diffusibility and signalling areas of the Wnt ligands Wnt8 and Wnt11. We found, using the Xenopus embryo, that Wnts do not diffuse effectively, whereas Frzb and Cres spread very widely. Interestingly, Frzb and Cres substantially promoted the diffusion of Wnt8 and Wnt11 through extracellular interactions. Importantly, we show that Wnt8 conveyed by sFRPs can activate canonical Wnt signalling despite the function of sFRPs as Wnt inhibitors, suggesting a novel regulatory system for Wnts by sFRPs.
Mii
Yusuke
Y
Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Taira
Masanori
M
D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D021381:Protein Transport; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D000099274:Frizzled-Related Proteins
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D051153:Wnt Proteins; D029867:Xenopus Proteins; D000099274:Frizzled-Related Proteins; C491629:frzb2 protein, Xenopus; C512785:wnt11b protein, Xenopus; C495248:wnt8a protein, Xenopus