Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion

Rui Sakuma, Yu Ichiro Ohnishi, Chikara Meno, Hideta Fujii, Hou Juan, Jun Takeuchi, Toshihiko Ogura, En Li, Kohei Miyazono, Hiroshi Hamada

研究成果: Contribution to journalArticle

149 被引用数 (Scopus)

抄録

Background: Two TGFβ-related proteins, Nodal and Lefty, are implicated in early embryonic patterning of vertebrates. Genetic data suggest that Nodal is a signalling molecule, while Lefty is an antagonist of Nodal, but their precise function remains unknown. Results: The signalling pathway of Nodal was investigated with the use of a Nodal-responsive assay system based on frog animal caps. Expression of dominant negative mutants of various receptors indicated that ALK4, and either ActRIIA or ActRIIB, function as type I and type II receptors for Nodal, respectively. A soluble form of Cripto lacking the COOH-terminal region interacted with Nodal but failed to mediate Nodal signalling, indicating that the native Cripto protein functions as a membrane-bound co-receptor for Nodal. Processed forms of Lefty proteins, both smaller and larger forms, inhibited Nodal signalling. Such Lefty-induced inhibition was rescued by excess ActRIIA or ActRIIB, suggesting that Lefty antagonizes Nodal signalling through competitive binding to the common receptor ActRIIA or ActRIIB. This idea was supported by the demonstration of a genetic interaction between lefty2 and ActRIIB in mouse. Behaviours of GFP-Nodal and GFP-Lefty2 proteins were also investigated in chick embryos. Both proteins could diffuse over a long distance, but the latter diffused faster than the former. Conclusions: Efficient inhibition of Nodal signals by Lefty may involve competitive binding of Lefty to the common receptors and faster diffusion of Lefty.

元の言語英語
ページ(範囲)401-412
ページ数12
ジャーナルGenes to Cells
7
発行部数4
DOI
出版物ステータス出版済み - 5 8 2002
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

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