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Related Experiment Videos

Tolloid gets Sizzled competing with Chordin.

Mary C Mullins1

  • 1Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Developmental Cell
|February 7, 2006
PubMed
Summary

Sizzled, a secreted Frizzled-related protein, surprisingly antagonizes BMP signaling, not Wnt pathways. It protects Chordin from cleavage by inhibiting a Tolloid-related metalloprotease, thereby limiting BMP activity.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Protein Signaling

Background:

  • Secreted Frizzled-related proteins (SFRPs) are typically Wnt signaling antagonists.
  • The specific function of Sizzled, an SFRP family member, remained unclear.
  • Understanding protein interactions in developmental pathways is crucial.

Purpose of the Study:

  • To elucidate the functional role of Sizzled.
  • To determine the signaling pathway(s) regulated by Sizzled.
  • To investigate the molecular mechanism of Sizzled action.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Analysis of Sizzled's effect on Wnt and BMP signaling pathways.
  • In vitro experiments investigating Sizzled's interaction with Chordin and Tolloid-related metalloproteases.

Main Results:

  • Sizzled does not function as a Wnt signaling antagonist.
  • Sizzled directly antagonizes Bone Morphogenetic Protein (BMP) signaling.
  • Sizzled competes with Chordin for binding to a Tolloid-related metalloprotease, preventing Chordin cleavage.

Conclusions:

  • Sizzled acts as a novel BMP signaling antagonist.
  • The mechanism involves protecting Chordin, a BMP inhibitor, from degradation.
  • This finding reveals a new layer of regulation in BMP signaling pathways.

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