title: F- and G-actin homeostasis regulates mechanosensitive actin nucleation by formins.
abstract: Physical force evokes rearrangement of the actin cytoskeleton. Signalling pathways such as tyrosine kinases, stretch-activated Ca(2+) channels and Rho GTPases are involved in force sensing. However, how signals are transduced to actin assembly remains obscure. Here we show mechanosensitive actin polymerization by formins (formin homology proteins). Cells overexpressing mDia1 increased the amount of F-actin on release of cell tension. Fluorescence single-molecule speckle microscopy revealed rapid induction of processive actin assembly by mDia1 on cell cortex deformation. mDia1 lacking the Rho-binding domain and other formins exhibited mechanosensitive actin nucleation, suggesting Rho-independent activation. Mechanosensitive actin nucleation by mDia1 required neither Ca(2+) nor kinase signalling. Overexpressing LIM kinase abrogated the induction of processive mDia1. Furthermore, s-FDAPplus (sequential fluorescence decay after photoactivation) analysis revealed a rapid actin monomer increase on cell cortex deformation. Our direct visualization of the molecular behaviour reveals a mechanosensitive actin filament regeneration mechanism in which G-actin released by actin remodelling plays a pivotal role.
authors: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
authors: Chiharu
authors: C
authors: Higashida
authors: Tai
authors: T
authors: Kiuchi
authors: Yushi
authors: Y
authors: Akiba
authors: Hiroaki
authors: H
authors: Mizuno
authors: Masahiro
authors: M
authors: Maruoka
authors: Shuh
authors: S
authors: Narumiya
authors: Kensaku
authors: K
authors: Mizuno
authors: Naoki
authors: N
authors: Watanabe
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D006706:Homeostasis; D006801:Humans; D007124:Immunoenzyme Techniques; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D013050:Spectrometry, Fluorescence; D014982:Xenopus laevis; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D020741:rho GTP-Binding Proteins; D002118:Calcium