Nodal stability determines signaling range

J. Ann Le Good, Katherine Joubin, Antonio J. Giraldez, Nadav Ben-Haim, Séverine Beck, Yu Chen, Alexander F. Schier, Daniel B. Constam

Research output: Contribution to journalArticlepeer-review

Abstract

Secreted TGFβ proteins of the Nodal family pattern the vertebrate body axes and induce mesoderm and endoderm [1]. Nodal proteins can act as morphogens [2], but the mechanisms regulating their activity and signaling range are poorly understood. In particular, it has been unclear how inefficient processing or rapid turnover of the Nodal protein influences autocrine and paracrine signaling properties [3, 4]. Here, we evaluate the role of Nodal processing and stability in tissue culture and zebrafish embryos. Removal of the pro domain potentiates autocrine signaling but reduces Nodal stability and signaling range. Insertion of an N-glycosylation site present in several related TGFβ proteins increases the stability of mature Nodal. The stabilized form of Nodal acts at a longer range than the wild-type form. These results suggest that increased proteolytic maturation of Nodal potentiates autocrine signaling, whereas increased Nodal stability extends paracrine signaling.

Original languageEnglish (US)
Pages (from-to)31-36
Number of pages6
JournalCurrent Biology
Volume15
Issue number1
DOIs
StatePublished - Jan 11 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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