Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1.
Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1.
复制标题
DOI：
10.1091/mbc.e12-05-0338
复制
发表时间：
2012-10
影响因子：
3.3
通讯作者：
Gundersen GG
中科院分区：
文献类型：
--
作者：
Bartolini F;Ramalingam N;Gundersen GG
肌动蛋白封端蛋白以一种依赖mDia1的方式诱导稳定的微管形成，并抑制mDia在生长的肌动蛋白丝末端的移位。通过小干扰RNA敲低封端蛋白会降低增殖细胞以及用溶血磷脂酸刺激的饥饿细胞中稳定微管的水平。
在迁移的成纤维细胞中，RhoA及其效应分子mDia1调节在迁移方向上极化的微管（MTs）的选择性稳定。mDia1的保守的成蛋白同源2结构域既参与肌动蛋白聚合又参与微管稳定，这两种活性之间的关系尚不清楚。我们发现，细胞松弛素A（LatA）和鬼笔环肽（jasplakinolide）这两种能使mDia1从肌动蛋白丝的倒刺端释放的肌动蛋白药物，刺激了血清饥饿的成纤维细胞中稳定微管的形成，并导致mDia1重新分布到微管上。通过小干扰RNA（siRNA）敲低mDia1可阻止LatA诱导稳定微管形成，而阻断上游的Rho或整合素信号通路则没有影响。在寻找mDia1的生理调节因子时，我们发现肌动蛋白封端蛋白以一种依赖mDia1的方式诱导稳定微管形成，并抑制mDia在生长的肌动蛋白丝末端的移位。通过siRNA敲低封端蛋白会降低增殖细胞以及用溶血磷脂酸刺激的饥饿细胞中稳定微管的水平。这些结果表明，肌动蛋白封端蛋白是一种新的微管稳定性调节因子，其通过拮抗mDia1对肌动蛋白丝的活性发挥作用，并提示了一种新的肌动蛋白 - 微管相互作用形式，即单个因子依次作用于肌动蛋白和微管。
Actin-capping protein induced stable microtubules in an mDia1-dependent manner and inhibited the translocation of mDia on the ends of growing actin filaments. Knockdown of capping protein by small interfering RNA reduced stable microtubule levels in proliferating cells and in starved cells stimulated with lysophosphatidic acid. In migrating fibroblasts, RhoA and its effector mDia1 regulate the selective stabilization of microtubules (MTs) polarized in the direction of migration. The conserved formin homology 2 domain of mDia1 is involved both in actin polymerization and MT stabilization, and the relationship between these two activities is unknown. We found that latrunculin A (LatA) and jasplakinolide, actin drugs that release mDia1 from actin filament barbed ends, stimulated stable MT formation in serum-starved fibroblasts and caused a redistribution of mDia1 onto MTs. Knockdown of mDia1 by small interfering RNA (siRNA) prevented stable MT induction by LatA, whereas blocking upstream Rho or integrin signaling had no effect. In search of physiological regulators of mDia1, we found that actin-capping protein induced stable MTs in an mDia1-dependent manner and inhibited the translocation of mDia on the ends of growing actin filaments. Knockdown of capping protein by siRNA reduced stable MT levels in proliferating cells and in starved cells stimulated with lysophosphatidic acid. These results show that actin-capping protein is a novel regulator of MT stability that functions by antagonizing mDia1 activity toward actin filaments and suggest a novel form of actin–MT cross-talk in which a single factor acts sequentially on actin and MTs.