Loss of γ-cytoplasmic actin triggers myofibroblast transition of human epithelial cells.
Bottom Line: Such epithelial plasticity is accompanied by dramatic reorganizations of the actin cytoskeleton, although mechanisms underlying cytoskeletal effects on epithelial transdifferentiation remain poorly understood.Induction of EMyT in γ-CYA-depleted cells depended on activation of serum response factor and its cofactors, myocardial-related transcriptional factors A and B.Loss of γ-CYA stimulated formin-mediated actin polymerization and activation of Rho GTPase, which appear to be essential for EMyT induction.
Affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298.Show MeSH
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Mentions: Formin-dependent actin polymerization is controlled by a small GTPase, RhoA (Goode and Eck, 2007). Furthermore, RhoA was shown to be essential for activation of an SRF/MRTF-dependent transcriptional program (Sotiropoulos et al., 1999; Mack et al., 2001; Miralles et al., 2003). Thus we next investigated the involvement of this GTPase in the observed EMyT response by using a Rho activation assay and inhibition of Rho signaling. Loss of γ-CYA resulted in a more than threefold increase in the amount of active RhoA without significant changes in total Rho expression (Figure 8, A and B). Furthermore Y27632, which is known to inhibit Rho-associated kinase (ROCK), suppressed induction of contractile proteins and assembly of F-actin bundles in γ-CYA–depleted A549 cells (Figure 8, C–E). Overall these results strongly suggest that Rho activation is essential for the EMyT induction caused by γ-CYA deficiency.
Affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298.