Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling.
Stem cell factor (SCF) and erythropoietin are strictly required for preventing apoptosis and stimulating proliferation, allowing the differentiation of erythroid precursors from colony-forming unit-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. Therefore, in this differentiation system, final maturation occurs independently of SCF signaling through caspase-induced ROCK-1 kinase activation.
Université René Descartes Paris V, CNRS UMR 8147 et IFR Necker, Paris, France.
A-S
AS
Gabet
S
S
Coulon
A
A
Fricot
J
J
Vandekerckhove
Y
Y
Chang
J-A
JA
Ribeil
L
L
Lordier
Y
Y
Zermati
V
V
Asnafi
Z
Z
Belaid
N
N
Debili
W
W
Vainchenker
B
B
Varet
O
O
Hermine
G
G
Courtois
D053148:Caspase 3 / Q000378:metabolism*; D002454:Cell Differentiation; D048429:Cell Size; D002843:Chromatin / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D004900:Erythroblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D024462:Myosin Type II / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D016207:Cytokines; D034741:RNA, Small Interfering; D019089:Stem Cell Factor; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D053148:Caspase 3; D024462:Myosin Type II; D020741:rho GTP-Binding Proteins