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Pan J.,Institute National Of La Sante Et Of La Recherche Medicale Unite 1009 | Pan J.,Institute Gustave Roussy | Pan J.,University Paris - Sud | Lordier L.,Institute National Of La Sante Et Of La Recherche Medicale Unite 1009 | And 22 more authors.
Blood | Year: 2014

Megakaryocytes are highly specialized precursor cells that produce platelets via cytoplasmic extensions called proplatelets. Proplatelet formation (PPF) requires profound changes in microtubule and actin organization. In this work, we demonstrated that DIAPH1 (mDia1), a mammalian homolog of Drosophila diaphanous that works as an effector of the small GTPase Rho, negatively regulates PPFby controlling the dynamics of the actin and microtubule cytoskeletons. Moreover, we showed that inhibition of both DIAPH1 and the Rho-associated protein kinase (Rock)/myosin pathway increased PPFvia coordination of both cytoskeletons. Weprovide evidence that 2 major effectors of the Rho GTPase pathway (DIAPH1 and Rock/myosin II) are involved not only in Rho-mediated stress fibers assembly, but also in the regulation of microtubule stability and dynamics during PPF. © 2014 by The American Society of Hematology.

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