The TGF-β co-receptor, CD109, promotes internalization and degradation of TGF-β receptors

Albane A Bizet1, Kai Liu, Nicolas Tran-Khanh

  • 1Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, QC, Canada.

Insights

CD109, a transforming growth factor-β (TGF-β) co-receptor, regulates TGF-β receptor endocytosis and degradation. This mechanism inhibits TGF-β signaling, impacting various pathological disorders like cancer.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Cancer research

Background:

  • Transforming growth factor-β (TGF-β) signaling is crucial in numerous diseases, including cancer.
  • TGF-β receptor endocytosis pathways (clathrin-coated pits vs. caveolae) differentially regulate signaling and degradation.
  • CD109 was previously identified as a TGF-β co-receptor and negative regulator of TGF-β signaling.

Purpose of the Study:

  • To elucidate the mechanism by which CD109 regulates TGF-β receptor trafficking and signaling.
  • To investigate the association between CD109, caveolae, and TGF-β receptor endocytosis.

Main Methods:

  • Co-immunoprecipitation to assess CD109 and caveolin-1 association.
  • Confocal microscopy to visualize receptor localization.
  • Ligand-binding assays and receptor degradation studies.

Main Results:

  • CD109 associates with caveolin-1, a key component of caveolae.
  • CD109 enhances TGF-β binding to its receptors and promotes their caveolae-mediated internalization.
  • CD109 facilitates TGF-β receptor localization within caveolae and subsequent degradation, thereby inhibiting signaling.

Conclusions:

  • CD109 acts as a negative regulator of TGF-β signaling by modulating receptor endocytosis and degradation via the caveolae pathway.
  • Targeting CD109-mediated endocytosis could offer therapeutic strategies for TGF-β-related pathologies, including cancer.

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