title: The formin DIAPH1 (mDia1) regulates megakaryocyte proplatelet formation by remodeling the actin and microtubule cytoskeletons.
abstract: 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.
authors.affiliation: 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;
authors.forename: Jiajia
authors.initials: J
authors.lastname: Pan
authors.affiliation: 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;
authors.forename: Larissa
authors.initials: L
authors.lastname: Lordier
authors.affiliation: 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;
authors.forename: Deborah
authors.initials: D
authors.lastname: Meyran
authors.affiliation: Institut Gustave Roussy, Plateforme Imagerie et Cytométrie, Villejuif, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Rameau
authors.affiliation: Institut Gustave Roussy, Plateforme Imagerie et Cytométrie, Villejuif, France;
authors.forename: Yann
authors.initials: Y
authors.lastname: Lecluse
authors.affiliation: Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI; and.
authors.forename: Susan
authors.initials: S
authors.lastname: Kitchen-Goosen
authors.affiliation: 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;
authors.forename: Idinath
authors.initials: I
authors.lastname: Badirou
authors.affiliation: 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;
authors.forename: Hayat
authors.initials: H
authors.lastname: Mokrani
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan.
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.affiliation: Laboratory of Cell Structure and Signal Integration, Van Andel Research Institute, Grand Rapids, MI; and.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Alberts
authors.affiliation: 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;
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.affiliation: 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;
authors.forename: Yunhua
authors.identifier: http://orcid.org/0000-0001-7160-6569
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism*; D000080865:Formins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008533:Megakaryocytes / Q000166:cytology*; D008870:Microtubules / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013926:Thrombopoietin / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018952:Antigens, CD34; C108962:DIAPH1 protein, human; D000080865:Formins; D034741:RNA, Small Interfering; D014404:Tubulin; D013926:Thrombopoietin; D020558:GTP Phosphohydrolases; D024462:Myosin Type II