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Coco is a dual activity modulator of TGFβ signaling

Alessia Deglincerti1, Tomomi Haremaki1, Aryeh Warmflash2

  • 1Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA.

Development (Cambridge, England)
|June 28, 2015
PubMed

Insights

Coco, a BMP/Activin/Nodal inhibitor, unexpectedly enhances TGFβ1 signaling by binding to TGFβ1 and its receptor. This dual role necessitates a reevaluation of TGFβ signaling regulation.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Transforming growth factor beta (TGFβ) signaling is vital for development and disease.
  • Soluble inhibitors regulate TGFβ ligand activity by blocking ligand-receptor interactions.

Purpose of the Study:

  • To identify novel regulators of ligand-dependent TGFβ signaling.
  • To investigate the unexpected role of Coco in TGFβ1 signaling.

Main Methods:

  • Genome-wide RNA interference (RNAi) screen.
  • Cell culture experiments.
  • Xenopus explant assays.

Main Results:

  • Coco was identified as an enhancer of TGFβ1 signaling.
  • Coco synergizes with TGFβ1 in both cell culture and Xenopus models.
  • Coco binds to TGFβ1, promoting its interaction with the Alk5 receptor.

Conclusions:

  • Coco exhibits context-dependent functions, acting as both an inhibitor and enhancer of signaling.
  • The findings challenge current models and call for a revised understanding of TGFβ pathway regulation.
Keywords:
CocoDual-activity pathway modulatorsTGFβ signaling modulators

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