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PMID:11029007

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Citation

Tamai, K, Semenov, M, Kato, Y, Spokony, R, Liu, C, Katsuyama, Y, Hess, F, Saint-Jeannet, JP and He, X (2000) LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530-5

Abstract

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex.

Links

PubMed Online version:10.1038/35035117

Keywords

Animals; Cloning, Molecular; Drosophila Proteins; Frizzled Receptors; Humans; Low Density Lipoprotein Receptor-Related Protein-6; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Neural Crest/metabolism; Proto-Oncogene Proteins/metabolism; Receptors, G-Protein-Coupled; Receptors, LDL/metabolism; Recombinant Fusion Proteins; Signal Transduction; Wnt Proteins; Wnt1 Protein; Xenopus; Xenopus Proteins; Zebrafish Proteins

Significance

Annotations

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

HUMAN:LRP6

part_of

GO:1990851: Wnt-Frizzled-LRP5/6 complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61091

C

Seeded From UniProt

complete

HUMAN:LRP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04426

F

Seeded From UniProt

complete

HUMAN:LRP6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61091

F

Seeded From UniProt

complete

HUMAN:LRP6

involved_in

GO:0014033: neural crest cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LRP6

involved_in

GO:0014029: neural crest formation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LRP6

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P04426

F

Seeded From UniProt

complete

HUMAN:LRP6

enables

GO:0005109: frizzled binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q61091

F

Seeded From UniProt

complete

HUMAN:LRP6

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LRP6

enables

GO:0071936: coreceptor activity involved in Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:LRP6

involved_in

GO:0044335: canonical Wnt signaling pathway involved in neural crest cell differentiation

ECO:0000305: curator inference used in manual assertion

GO:0014033

P

Seeded From UniProt

complete

MOUSE:WNT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75581

F

Seeded From UniProt

complete

XENLA:WNT3A

involved_in

GO:0014033: neural crest cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

XENLA:WNT5A

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FZD8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75581

F

Seeded From UniProt

complete

HUMAN:FZD5

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LRP5

involved_in

GO:0060070: canonical Wnt signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FZD8

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75581

F

Seeded From UniProt

complete

MOUSE:FZD8

part_of

GO:1990851: Wnt-Frizzled-LRP5/6 complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O75581

C

Seeded From UniProt

complete


See also

References

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