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PMID:19906850

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Citation

Mii, Y and Taira, M (2009) Secreted Frizzled-related proteins enhance the diffusion of Wnt ligands and expand their signalling range. Development 136:4083-8

Abstract

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.

Links

PubMed Online version:10.1242/dev.032524

Keywords

Animals; Embryo, Nonmammalian/embryology; Embryo, Nonmammalian/metabolism; Female; Gastrula/metabolism; Gene Expression Regulation, Developmental; Glycoproteins/genetics; Glycoproteins/secretion; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism; Ligands; Protein Transport; Signal Transduction; Wnt Proteins/genetics; Wnt Proteins/metabolism; Xenopus Proteins/genetics; Xenopus Proteins/metabolism; Xenopus laevis/embryology; Xenopus laevis/genetics; Xenopus laevis/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

XENLA:WNT8

colocalizes_with

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:WNT8

located_in

GO:0062023: collagen-containing extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:WNT8

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:WN11B

located_in

GO:0062023: collagen-containing extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:Q32N13

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:Q32N13

involved_in

GO:0035593: positive regulation of Wnt signaling pathway by establishment of Wnt protein localization to extracellular region

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P28026)

Seeded From UniProt

complete

XENLA:WN11B

part_of

GO:0062023: collagen-containing extracellular matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:WN11B

colocalizes_with

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

XENLA:WN11B

involved_in

GO:0035567: non-canonical Wnt signaling pathway

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete


See also

References

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