Schwann cells in the sciatic nerve express high levels of low density lipoprotein receptor-related protein (LRP1) only after undergoing phenotypic transformation in nerve injury. Schwann cells in culture also express abundant LRP1, providing a model of Schwann cells in the injured nerve. In this study, we show that LRP1 gene-silencing or treatment of Schwann cells with the LRP1 antagonist, receptor-associated protein (RAP), promotes cell adhesion and substantially inhibits cell migration on fibronectin-coated surfaces. When allowed to adhere to fibronectin, LRP1 gene-silenced cells form well-defined focal adhesions and bundle f-actin into prominent stress fibers more rapidly than control cells. These changes reflect a substantially increased level of activated RhoA and decreased activation of Rac1 in Schwann cells in which LRP1 is absent or neutralized. LRP1 ligands, including matrix metalloprotease-9, tissue-type plasminogen activator and α2-macro-globulin activated Rac1 in control Schwann cells. A pharmacologic inhibitor of Rac1 activation promoted adhesion of control Schwann cells whereas Rho kinase inhibitor promoted migration and inhibited adhesion of LRP1 gene-silenced cells. These results define LRP1 as a receptor that controls Schwann cell adhesion and migration by its effects on the activity of small Rho family GTPases. LRP1 expression transforms the Schwann cell phenotype from immobile to migratory.
Rac1 and RhoA are regulated reciprocally downstream of low density lipoprotein receptor-related protein (LRP1) to control Schwann cell adhesion and migration / Mantuano, Elisabetta; Jo, M; Gonias, Sl; Campana, W. M.. - STAMPA. - (2010). (Intervento presentato al convegno Gordon Research Conferences 2010 tenutosi a Ventura, CA. USA nel Feb 10-15).
Rac1 and RhoA are regulated reciprocally downstream of low density lipoprotein receptor-related protein (LRP1) to control Schwann cell adhesion and migration
MANTUANO, ELISABETTA;
2010
Abstract
Schwann cells in the sciatic nerve express high levels of low density lipoprotein receptor-related protein (LRP1) only after undergoing phenotypic transformation in nerve injury. Schwann cells in culture also express abundant LRP1, providing a model of Schwann cells in the injured nerve. In this study, we show that LRP1 gene-silencing or treatment of Schwann cells with the LRP1 antagonist, receptor-associated protein (RAP), promotes cell adhesion and substantially inhibits cell migration on fibronectin-coated surfaces. When allowed to adhere to fibronectin, LRP1 gene-silenced cells form well-defined focal adhesions and bundle f-actin into prominent stress fibers more rapidly than control cells. These changes reflect a substantially increased level of activated RhoA and decreased activation of Rac1 in Schwann cells in which LRP1 is absent or neutralized. LRP1 ligands, including matrix metalloprotease-9, tissue-type plasminogen activator and α2-macro-globulin activated Rac1 in control Schwann cells. A pharmacologic inhibitor of Rac1 activation promoted adhesion of control Schwann cells whereas Rho kinase inhibitor promoted migration and inhibited adhesion of LRP1 gene-silenced cells. These results define LRP1 as a receptor that controls Schwann cell adhesion and migration by its effects on the activity of small Rho family GTPases. LRP1 expression transforms the Schwann cell phenotype from immobile to migratory.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.