Journal
GENES TO CELLS
Volume 24, Issue 5, Pages 390-402Publisher
WILEY
DOI: 10.1111/gtc.12682
Keywords
keratin; mechanotransduction; Rho-GEF; Solo; stress fiber; traction force; wrinkle assay
Categories
Funding
- Japan Society for the Promotion of Science [JP15H03004, JP15K14469, JP16H00749, JP16H05907, JP16K07335, JP16K12872, JP18K19280, JP23112005, JPA16J041330, JPT17K151180]
- Japan Agency for Medical Research and Development [JP17gm5810015]
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Solo (ARHGEF40) is a RhoA-targeting guanine nucleotide exchange factor that regulates tensional force-induced cytoskeletal reorganization. Solo binds to keratin 8/keratin 18 (K8/K18) filaments through multiple sites, but the roles of these interactions in the localization and mechanotransduction-regulating function of Solo remain unclear. Here, we constructed two Solo mutants (L14R/L17R and L49R/L52R) with leucine-to-arginine replacements in the N-terminal conserved region (which we termed the Solo domain) and analyzed their K18-binding activities. These mutations markedly decreased the K18-binding ability of the N-terminal fragment (residues 1-329) of Solo but had no apparent effect on the K18-binding ability of full-length (FL) Solo. When expressed in cultured cells, wild-type Solo-FL showed a unique punctate localization near the ventral surface of cells and caused the reinforcement of actin filaments. In contrast, despite retaining the K18-binding ability, the L14R/L17R and L49R/L52R mutants of Solo-FL were diffusely distributed in the cytoplasm and barely induced actin cytoskeletal reinforcement. Furthermore, wild-type Solo-FL promoted traction force generation against extracellular matrices and tensional force-induced stress fiber reinforcement, but its L14R/L17R and L49R/L52R mutants did not. These results suggest that the K18-binding ability of the N-terminal Solo domain is critical for the ventral localization of Solo and its function in regulating mechanotransduction.
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