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Related Experiment Videos

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
Summary
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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:

Related Experiment Videos

  • 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.