title: Interplay between Solo and keratin filaments is crucial for mechanical force-induced stress fiber reinforcement.
abstract: Mechanical force-induced 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 stretch-induced 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 force-induced 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 force-induced RhoA activation and consequent actin cytoskeletal reinforcement.
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Fujiwara
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan kohashi@biology.tohoku.ac.jp kmizuno@biology.tohoku.ac.jp.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Mashiko
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan kohashi@biology.tohoku.ac.jp kmizuno@biology.tohoku.ac.jp.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism*; D053533:Keratin-8 / Q000378:metabolism*; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism*; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
chemical_list: C505620:ARHGEF40 protein, human; D020662:Guanine Nucleotide Exchange Factors; D053538:Keratin-18; D053533:Keratin-8; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
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