| First Author | Loubet D | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 2 | Pages | 678-90 |
| PubMed ID | 22038049 | Mgi Jnum | J:180619 |
| Mgi Id | MGI:5306711 | Doi | 10.1096/fj.11-185579 |
| Citation | Loubet D, et al. (2012) Neuritogenesis: the prion protein controls beta1 integrin signaling activity. FASEB J 26(2):678-90 |
| abstractText | Cytoskeleton modifications are required for neuronal stem cells to acquire neuronal polarization. Little is known, however, about mechanisms that orchestrate cytoskeleton remodeling along neuritogenesis. Here, we show that the silencing of the cellular prion protein (PrP(C)) impairs the initial sprouting of neurites upon induction of differentiation of the 1C11 neuroectodermal cell line, indicating that PrP(C) is necessary to neuritogenesis. Such PrP(C) function relies on its capacity to negatively regulate the clustering, activation, and signaling activity of beta1 integrins at the plasma membrane. beta1 Integrin aggregation caused by PrP(C) depletion triggers overactivation of the RhoA-Rho kinase-LIMK-cofilin pathway, which, in turn, alters the turnover of focal adhesions, increases the stability of actin microfilaments, and in fine impairs neurite formation. Inhibition of Rho kinases is sufficient to compensate for the lack of PrP(C) and to restore neurite sprouting. We also observe an increased secretion of fibronectin in the surrounding milieu of PrP(C)-depleted 1C11 cells, which likely self-sustains beta1 integrin signaling overactivation and contributes to neuritogenesis defect. Our overall data reveal that PrP(C) contributes to the acquisition of neuronal polarization by modulating beta1 integrin activity, cell interaction with fibronectin, and cytoskeleton dynamics.-Loubet, D., Dakowski, C., Pietri, M., Pradines, E., Bernard, S., Callebert, J., Ardila-Osorio, H., Mouillet-Richard, S., Launay, J. M., Kellermann, O., Schneider, B. Neuritogenesis: the prion protein controls beta1 integrin signaling activity. |
