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The prion protein inhibits monocytic cell migration by stimulating β1 integrin adhesion and uropod formation

Dion D Richardson1, Simon Tol1, Eider Valle-Encinas1

  • 1Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, The Netherlands.

Journal of Cell Science
|July 11, 2015
PubMed

Insights

The prion protein (PrP) regulates monocyte adhesion and migration by influencing β1-integrin activation and cell shape. PrP controls key proteins involved in cell movement and linkage, impacting monocyte behavior.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • The glycosylphosphatidylinositol (GPI)-anchored prion protein (PrP) is widely distributed and conserved, suggesting a role in cellular homeostasis.
  • PrP's proposed function in cell adhesion may explain various effects of PrP loss-of-function, including immune phenotypes in PrP knockout mice.

Purpose of the Study:

  • To investigate the role of PrP in the adhesion and transendothelial migration of human (pro)monocytes.
  • To elucidate the molecular mechanisms by which PrP influences monocyte behavior.

Main Methods:

  • Investigated PrP's role in monocyte adhesion and migration using PrP-silenced cells.
  • Analyzed the impact of PrP on β1-integrin-mediated adhesion, cell morphology, and migration.
  • Examined the regulation of proteins involved in cell adhesion and migration, including RhoA, cofilin, and ERM family proteins.

Main Results:

  • PrP was found to regulate β1-integrin-mediated adhesion of monocytes.
  • PrP silencing led to deficient uropod formation and altered cell protrusions during migration.
  • PrP controls ligand-induced integrin activation and modulates RhoA, cofilin, and ERM protein activity.

Conclusions:

  • PrP plays a crucial role in regulating monocyte adhesion and migration.
  • PrP modulates monocyte behavior through RhoA-induced actin remodeling and ERM-mediated membrane-cytoskeleton linkage.
  • These findings highlight PrP as a key regulator of immune cell dynamics.
Keywords:
AdhesionERMMigrationMonocytePrion proteinRhoA

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