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Nodal stability determines signaling range

J Ann Le Good1, Katherine Joubin, Antonio J Giraldez

  • 1Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.

Current Biology : CB
|January 15, 2005
PubMed

Insights

Nodal protein processing and stability critically influence its signaling. Enhanced maturation boosts autocrine signals, while increased stability extends its paracrine range, impacting body axis formation.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • Secreted TGFbeta proteins of the Nodal family are crucial for patterning vertebrate body axes and inducing mesoderm/endoderm.
  • Nodal proteins function as morphogens, but mechanisms controlling their activity and signaling range remain unclear.
  • The impact of Nodal processing and protein turnover on autocrine and paracrine signaling is poorly understood.

Purpose of the Study:

  • To investigate the role of Nodal protein processing and stability in regulating its signaling properties.
  • To determine how modifications affecting Nodal maturation and turnover influence its autocrine and paracrine functions.
  • To elucidate the relationship between Nodal processing, stability, and its morphogenetic activity in vivo and in vitro.

Main Methods:

  • Experiments were conducted in tissue culture and zebrafish embryos.
  • Nodal protein processing was manipulated, including pro domain removal.
  • N-glycosylation sites were introduced to modulate Nodal stability.

Main Results:

  • Removal of the Nodal pro domain enhanced autocrine signaling but decreased protein stability and signaling range.
  • Introducing an N-glycosylation site increased mature Nodal stability and extended its signaling range.
  • Stabilized Nodal variants demonstrated longer-range activity compared to wild-type Nodal.

Conclusions:

  • Proteolytic maturation of Nodal potentiates autocrine signaling.
  • Increased Nodal stability extends its paracrine signaling range.
  • Nodal processing and stability are key regulators of its morphogenetic functions.

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