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Updated: Jun 21, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
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Endothelial cell protein C receptor cellular localization and trafficking: potential functional implications.

Ramesh C Nayak1, Prosenjit Sen, Samit Ghosh

  • 1Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.

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|July 10, 2009
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Endothelial cell protein C receptor (EPCR) binding to Factor VIIa or activated protein C triggers EPCR internalization. This receptor-mediated endocytosis aids in FVIIa clearance from circulation.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Endothelial cell protein C receptor (EPCR) binding to ligands is biochemically understood.
  • The impact of cell surface EPCR-ligand interactions on its cellular trafficking remains unclear.

Purpose of the Study:

  • To characterize the cellular localization and trafficking of EPCR in endothelial cells.
  • To investigate the role of EPCR-ligand interactions in EPCR internalization and subsequent cellular transport.

Main Methods:

  • Immunofluorescence confocal microscopy in endothelial cells and a heterologous system.
  • Studies on EPCR localization in caveolin-1 positive membrane microdomains.
  • Analysis of EPCR and ligand endocytosis via dynamin- and caveolar-dependent pathways.
  • In vivo studies using EPCR-blocking antibodies in mice.

Main Results:

  • EPCR is primarily located on the cell surface in caveolin-1 positive microdomains, with a fraction in intracellular recycling compartments.
  • Binding of Factor VIIa (FVIIa) or activated protein C induces rapid EPCR endocytosis via a caveolar pathway.
  • Endocytosed EPCR-ligand complexes are recycled to the cell surface and facilitate FVIIa transcytosis.
  • In vivo blockade of EPCR impairs early FVIIa clearance.

Conclusions:

  • Ligand binding promotes EPCR endocytosis and recycling.
  • EPCR-mediated endocytosis facilitates FVIIa transcytosis and circulatory clearance.