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Ligand-dependent and -independent transforming growth factor-beta receptor recycling regulated by clathrin-mediated

Hugh Mitchell1, Amit Choudhury, Richard E Pagano

  • 1Thoracic Diseases Research Unit, Department of Biochemistry and Molecular Biology and Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN 55905, USA.

Molecular Biology of the Cell
|July 2, 2004
PubMed

Insights

Transforming growth factor-beta (TGF-beta) receptors recycle via clathrin-coated pits, independent of ligand binding. This recycling pathway, dependent on rab11, directs activated receptors for degradation after ligand binding.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Protein trafficking

Background:

  • Transforming growth factor-beta (TGF-beta) signaling involves transmembrane serine/threonine kinases (type I and type II receptors).
  • Ligand binding to TGF-beta receptors leads to signaling and receptor down-regulation.
  • Previous research focused on TGF-beta signaling pathways, with recent interest in receptor trafficking.

Purpose of the Study:

  • To investigate the trafficking properties of TGF-beta receptors.
  • To determine if TGF-beta receptor recycling is ligand-dependent.
  • To elucidate the mechanism and pathway involved in TGF-beta receptor internalization and recycling.

Main Methods:

  • Analysis of TGF-beta receptor internalization and recycling rates.
  • Investigation of receptor trafficking in the presence and absence of ligand.
  • Utilizing clathrin-coated pits and rab GTPases (rab11, rab4) to study the recycling pathway.

Main Results:

  • TGF-beta receptors undergo recycling irrespective of ligand activation.
  • Ligand binding does not alter the rates of receptor internalization or recycling.
  • Receptor internalization occurs via clathrin-coated pits, with rab11-dependent and rab4-independent recycling to the plasma membrane.

Conclusions:

  • TGF-beta receptor recycling is a continuous process, not solely triggered by ligand binding.
  • Activated TGF-beta receptors are routed to a specific endocytic pathway for degradation.
  • This pathway involves multiple rounds of recycling before clathrin-dependent degradation.

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