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Intracellular trafficking of transforming growth factor β receptors

Ihor Yakymovych1, Mariya Yakymovych1, Carl-Henrik Heldin1

  • 1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala 75123, Sweden.

Acta Biochimica Et Biophysica Sinica
|November 30, 2017
PubMed

Insights

Transforming growth factor β (TGFβ) receptor trafficking controls cell surface availability and signaling. Proper intracellular transport and localization are crucial for TGFβ pathway regulation and preventing disease.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Receptor trafficking

Background:

  • Transforming growth factor β (TGFβ) signaling is mediated by type I (TβRI) and type II (TβRII) kinase receptors.
  • Receptor availability at the cell surface is tightly regulated through synthesis, transport, and internalization.
  • Dysregulation of TGFβ receptor localization is linked to human diseases.

Purpose of the Study:

  • To elucidate the mechanisms controlling TGFβ receptor intracellular trafficking.
  • To understand the role of trafficking in TGFβ signaling pathways.
  • To highlight the clinical relevance of receptor localization.

Main Methods:

  • Investigated receptor delivery from the Golgi to the cell surface.
  • Examined cell surface distribution and microdomain localization.
  • Studied clathrin- and caveolae-mediated endocytosis pathways.
  • Assessed the impact of endocytosis on Smad and non-Smad signaling.
  • Correlated receptor mislocalization with clinical data.

Main Results:

  • TβRI and TβRII utilize distinct routes for cell surface delivery.
  • Receptors are compartmentalized within plasma membrane microdomains.
  • Endocytosis, while not essential for all TGFβ signaling, influences Smad activation via early endosomes.
  • Caveolae-mediated endocytosis is critical for non-Smad TGFβ signaling.
  • Receptor mislocalization is observed in several human diseases.

Conclusions:

  • Intracellular trafficking is a key regulatory point for TGFβ receptor function.
  • Distinct endocytic pathways differentially impact TGFβ signaling.
  • Precise control of TGFβ receptor trafficking, expression, and degradation is vital for cellular homeostasis.
  • Understanding receptor trafficking offers insights into disease pathogenesis and potential therapeutic strategies.
Keywords:
TGFβ receptorclathrinendocytosisendosomelipid rafts

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