LDL-receptor-related proteins in Wnt signal transduction

被引：1078

作者：

Tamai, K

Semenov, M

Kato, Y

Spokony, R

Liu, CM

Katsuyama, Y

Hess, F

Saint-Jeannet, JP

He, X

机构：

[1] Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol,Div Neurosci, Boston, MA 02115 USA

[2] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA

[3] Merck Res Labs, Dept Human Genet, West Point, PA 19486 USA

来源：

NATURE | 2000年 / 407卷 / 6803期

关键词：

D O I：

10.1038/35035117

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation(1). The Frizzled (Fz) family of serpentine receptors function as Wnt receptors(2-10), but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype(11), and encodes a transmembrane protein(11) 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.

引用

页码：530 / 535

页数：7

共 31 条

[1] A new member of the frizzled family from Drosophila functions as a Wingless receptor [J].