Palazzo A F, Cook T A, Alberts A S, Gundersen G G
Department of Anatomy & Cell Biology, Columbia University, New York 10032, USA.
Nat Cell Biol. 2001 Aug;3(8):723-9. doi: 10.1038/35087035.
Rho-GTPase stabilizes microtubules that are oriented towards the leading edge in serum-starved 3T3 fibroblasts through an unknown mechanism. We used a Rho-effector domain screen to identify mDia as a downstream Rho effector involved in microtubule stabilization. Constitutively active mDia or activation of endogenous mDia with the mDia-autoinhibitory domain stimulated the formation of stable microtubules that were capped and oriented towards the wound edge. mDia co-localized with stable microtubules when overexpressed and associated with microtubules in vitro. Rho kinase was not necessary for the formation of stable microtubules. Our results show that mDia is sufficient to generate and orient stable microtubules, and indicate that Dia-related formins are part of a conserved pathway that regulates the dynamics of microtubule ends.
Rho-GTP酶通过一种未知机制稳定血清饥饿的3T3成纤维细胞中朝向前沿排列的微管。我们使用Rho效应结构域筛选来鉴定mDia作为参与微管稳定的下游Rho效应物。组成型活性mDia或用mDia自抑制结构域激活内源性mDia会刺激形成稳定的微管,这些微管被加帽并朝向伤口边缘排列。当mDia过表达时,它与稳定的微管共定位,并且在体外与微管相关联。稳定微管的形成不需要Rho激酶。我们的结果表明,mDia足以产生并定向稳定的微管,并表明与Dia相关的formin是调节微管末端动力学的保守途径的一部分。