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J Cell Sci. 2015 Aug 15;128(16):3018-29. doi: 10.1242/jcs.165365. Epub 2015 Jul 9.

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

Author information

1
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, The Netherlands.
2
Department of Plasma Proteins, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, The Netherlands.
3
Department of Pediatric Oncology/Hematology, Erasmus University Medical Center, Rotterdam 3015 CN, The Netherlands.
4
Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam 1066CX, The Netherlands m.fernandez@sanquin.nl.

Abstract

The broad tissue distribution and evolutionary conservation of the glycosylphosphatidylinositol (GPI)-anchored prion protein (PrP, also known as PRNP) suggests that it plays a role in cellular homeostasis. Given that integrin adhesion determines cell behavior, the proposed role of PrP in cell adhesion might underlie the various in vitro and in vivo effects associated with PrP loss-of-function, including the immune phenotypes described in PrP(-/-) mice. Here, we investigated the role of PrP in the adhesion and (transendothelial) migration of human (pro)monocytes. We found that PrP regulates β1-integrin-mediated adhesion of monocytes. Additionally, PrP controls the cell morphology and migratory behavior of monocytes: PrP-silenced cells show deficient uropod formation on immobilized VCAM and display bleb-like protrusions on the endothelium. Our data further show that PrP regulates ligand-induced integrin activation. Finally, we found that PrP controls the activation of several proteins involved in cell adhesion and migration, including RhoA and its effector cofilin, as well as proteins of the ERM family. We propose that PrP modulates β1 integrin adhesion and migration of monocytes through RhoA-induced actin remodeling mediated by cofilin, and through the regulation of ERM-mediated membrane-cytoskeleton linkage.

KEYWORDS:

Adhesion; ERM; Migration; Monocyte; Prion protein; RhoA

PMID:
26159734
DOI:
10.1242/jcs.165365
[Indexed for MEDLINE]
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