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Blood. 2014 Dec 18;124(26):3967-77. doi: 10.1182/blood-2013-12-544924. Epub 2014 Oct 8.

The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons.

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Institut National de la Santé et de la Recherche Médicale Unité 1009, Institut Gustave Roussy, Villejuif, France; Institut Gustave Roussy, Plateforme Imagerie et Cytométrie, Villejuif, France; Université Paris-Sud, Le Kremlin-Bicêtre, France;
Institut Gustave Roussy, Plateforme Imagerie et Cytométrie, Villejuif, France;
Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI; and.
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan.


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 PPF by 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 PPF via coordination of both cytoskeletons. We provide 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.

[Indexed for MEDLINE]

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