LDL-receptor-related proteins in Wnt signal transduction

Citation
K. Tamai et al., LDL-receptor-related proteins in Wnt signal transduction, NATURE, 407(6803), 2000, pp. 530-535
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary,Multidisciplinary,Multidisciplinary
Journal title
NATURE
ISSN journal
0028-0836 → ACNP
Volume
407
Issue
6803
Year of publication
2000
Pages
530 - 535
Database
ISI
SICI code
0028-0836(20000928)407:6803<530:LPIWST>2.0.ZU;2-2
Abstract
The Wnt family of secreted signalling molecules are essential in embryo dev elopment and tumour formation(1). The Frizzled (Fz) family of serpentine re ceptors function as Wnt receptors(2-10), but how Fz proteins transduce sign alling is not understood. In Drosophila, arrow phenocopies the wingless (DW nt-1) phenotype(11), and encodes a transmembrane protein(11) that is homolo gous 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 Xenopu s embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive gen es, dorsal axis duplication and neural crest formation. An LRP6 mutant lack ing the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest developm ent. 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.