Interplay between Solo and keratin filaments is crucial for mechanical forceinduced stress fiber reinforcement

Sachiko Fujiwara, Kazumasa Ohashi, Toshiya Mashiko, Hiroshi Kondo, Kensaku Mizuno

    Research output: Contribution to journalArticlepeer-review

    37 Citations (Scopus)


    Mechanical forceinduced cytoskeletal reorganization is essential for cell and tissue remodeling and homeostasis; however, the underlying cellular mechanisms remain elusive. Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor (GEF) involved in cyclical stretchinduced human endothelial cell reorientation and convergent extension cell movement in zebrafish gastrula. In this study, we show that Solo binds to keratin-8/keratin-18 (K8/K18) intermediate filaments through multiple sites. Solo overexpression promotes the formation of thick actin stress fibers and keratin bundles, whereas knockdown of Solo, expression of a GEF-inactive mutant of Solo, or inhibition of ROCK suppresses stress fiber formation and leads to disorganized keratin networks, indicating that the Solo-RhoA-ROCK pathway serves to precisely organize keratin networks, as well as to promote stress fibers. Of importance, knockdown of Solo or K18 or overexpression of GEF-inactive or deletion mutants of Solo suppresses tensile forceinduced stress fiber reinforcement. Furthermore, knockdown of Solo or K18 suppresses tensile force-induced RhoA activation. These results strongly suggest that the interplay between Solo and K8/K18 filaments plays a crucial role in tensile forceinduced RhoA activation and consequent actin cytoskeletal reinforcement.

    Original languageEnglish
    Pages (from-to)954-966
    Number of pages13
    JournalMolecular biology of the cell
    Issue number6
    Publication statusPublished - 2016 Mar 15

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology


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