| First Author | Richardson DD | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 16 | Pages | 3018-29 |
| PubMed ID | 26159734 | Mgi Jnum | J:233051 |
| Mgi Id | MGI:5780649 | Doi | 10.1242/jcs.165365 |
| Citation | Richardson DD, et al. (2015) The prion protein inhibits monocytic cell migration by stimulating beta1 integrin adhesion and uropod formation. J Cell Sci 128(16):3018-29 |
| abstractText | 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 beta1-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 beta1 integrin adhesion and migration of monocytes through RhoA-induced actin remodeling mediated by cofilin, and through the regulation of ERM-mediated membrane-cytoskeleton linkage. |
