CASPASE-ACTIVATED ROCK-1 ALLOWS ERYTHROBLAST TERMINAL MATURATION INDEPENDENTLY OF CYTOKINE-INDUCED RHO SIGNALING

Genevieve Courtois (1) , Anne Sophie Gabet (1) , Severine Coulon (1) , Julie Vandekerckhove (1) , Aurelie Fricot (1) , Jean-Antoine Ribeil (1) , Zakia Belaid (1) , Vahid Asnafi (1) , Yunhua Chang (1) , Larissa Lordier (1) , Najet Debili (1) , Yael Zermati (1) , William Vainchenker (1) , Bruno Varet (1) , Olivier Hermine (1)

1 UPD5 - Université Paris Descartes - Paris 5

Stem cell factor (SCF) and erythropoietin (EPO) are strictly required for preventing apoptosis and stimulating proliferation, allowing the differentiation of erythroid precursors from CFU-E to the polychromatophilic stage. In contrast, terminal maturation to generate reticulocytes occurs independently of cytokine signaling by a mechanism not fully understood. Terminal differentiation is characterized by a sequence of morphological changes including a progressive decrease in cell size, chromatin condensation in the nucleus and disappearance of organelles, which requires transient caspase activation. These events are followed by nucleus extrusion as a consequence of plasma membrane and cytoskeleton reorganization. Here we show that in early step, SCF stimulates the Rho/Rock pathway until the basophilic stage. Thereafter, Rock-1 is activated independently of Rho signaling by caspase-3-mediated cleavage, allowing terminal maturation at least in part through phosphorylation of the light chain of myosin II (MLC2). Therefore, in this differentiation system, final maturation occurs independently of SCF signaling through caspase-induced Rock-1 kinase activation.

Mots clés: erythropoiesis; Rock1; caspases

Genevieve Courtois, Anne Sophie Gabet, Severine Coulon, Julie Vandekerckhove, Aurelie Fricot, et al.. CASPASE-ACTIVATED ROCK-1 ALLOWS ERYTHROBLAST TERMINAL MATURATION INDEPENDENTLY OF CYTOKINE-INDUCED RHO SIGNALING. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.140⟩. ⟨hal-00592288⟩