The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons
| Autor: | Yann Lécluse, Jiajia Pan, I. Badirou, Hayat Mokrani, Susan M. Kitchen-Goosen, Arthur S. Alberts, Larissa Lordier, Shuh Narumiya, Yunhua Chang, Deborah Meyran, Philippe Rameau, William Vainchenker |
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| Rok vydání: | 2014 |
| Předmět: |
Blood Platelets
Immunology Formins Antigens CD34 macromolecular substances Microtubules Biochemistry GTP Phosphohydrolases Tubulin Microtubule Myosin Humans DIAPH1 Small GTPase Cloning Molecular RNA Small Interfering Cytoskeleton Actin Adaptor Proteins Signal Transducing Myosin Type II biology Chemistry Lentivirus Cell Differentiation Cell Biology Hematology Actins Cell biology Thrombopoietin biology.protein MDia1 Megakaryocytes |
| Zdroj: | Blood. 124:3967-3977 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-12-544924 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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