The formin homology protein mDia1 regulates dynamics of microtubules and their effect on focal adhesion growth

The formin homology protein, mDia1, is a major effector of Rho controlling, together with the Rho-kinase (ROCK), the formation of focal adhesions and stress fibers. Here we show that a constitutively active form of mDia1 (mDia1∆N3) affects the dynamics of microtubules at three stages of their life. We found that in cells expressing mDia1∆N3, (1) the growth rate at the microtubule plus-end decreased by half, (2) the rates of microtubule plus-end growth and shortening at the cell periphery decreased while the frequency of catastrophes and rescue events remained unchanged, and (3) mDia1∆N3 expression in cytoplasts without centrosome stabilized free microtubule minus-ends. This stabilization required the activity of another Rho target, ROCK. Interestingly, mDia1∆N3 as well as endogenous mDia1, localized at the centrosome. The changes in microtubule behavior in the mDia1∆N3-expressing cells increased both microtubule targeting toward focal adhesions, and their inhibitory effect on focal adhesion growth. Thus, mDia1induced alterations in microtubule dynamics augment the microtubule-mediated negative regulation of focal adhesions.