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Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion

2007; Cold Spring Harbor Laboratory Press; Volume: 21; Issue: 12 Linguagem: Inglês

10.1101/gad.424807

1549-5477

Thomas Kitzing, Arul S. Sahadevan, Dominique T. Brandt, Helga Knieling, Sebastian Hannemann, O. Fackler, Jörg Großhans, Robert Grosse,

Microtubule and mitosis dynamics

The RhoA-effector Dia1 controls actin-dependent processes such as cytokinesis, SRF transcriptional activity, and cell motility. Dia1 polymerizes actin through its formin homology (FH) 2 domain. Here we show that Dia1 acts upstream of RhoA independently of its effects on actin assembly. Dia1 binds to the leukemia-associated Rho-GEF (LARG) through RhoA-dependent release of Dia1 autoinhibition. The FH2 domain stimulates the guanine nucleotide exchange activity of LARG in vitro. Our results reveal that Dia1 is necessary for LPA-stimulated Rho/ROCK signaling and bleb-associated cancer cell invasion. Thus, Dia1-dependent RhoA activation constitutes a positive feedback mechanism to modulate cell behavior.