The formin mDia2 stabilizes microtubules independently of its actin nucleation activity.
The formin mDia2 stabilizes microtubules independently of its actin nucleation activity.
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Formin MDIA2独立于其肌动蛋白成核活性稳定微管。
DOI：
10.1083/jcb.200709029
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发表时间：
2008-05-05
影响因子：
7.8
通讯作者：
Gundersen, Gregg G.
中科院分区：
文献类型：
--
作者：
Bartolini, Francesca;Moseley, James B.;Schmoranzer, Jan;Cassimeris, Lynne;Goode, Bruce L.;Gundersen, Gregg G.
细胞迁移中一个关键的微管（MT）极化事件是依赖于Rho/mDia对朝向迁移方向的一部分微管进行稳定。尽管mDia能使肌动蛋白丝成核，但不清楚是这种作用还是mDia的另一种独立活性是微管稳定的基础。我们在含有成蛋白同源结构域1和2（FH1FH2）的组成型活性形式的mDia2中产生了两个肌动蛋白突变体（K853A和I704A），发现它们仍然能诱导稳定的微管，并与微管末端结合蛋白EB1和APC结合，而EB1和APC也与微管稳定有关。mDia2的一个二聚化受损突变体（W630A）在细胞中也能产生稳定的微管。我们检测了FH1FH2 - mDia2在体外是否对微管有直接活性，发现它能直接与微管结合，稳定微管以抵抗冷诱导和稀释诱导的解聚，并且分别降低微管组装和解聚过程中的生长和缩短速率。这些结果表明mDia2具有一种新的微管稳定活性，这种活性与其肌动蛋白成核活性是分开的。
A critical microtubule (MT) polarization event in cell migration is the Rho/mDia-dependent stabilization of a subset of MTs oriented toward the direction of migration. Although mDia nucleates actin filaments, it is unclear whether this or a separate activity of mDia underlies MT stabilization. We generated two actin mutants (K853A and I704A) in a constitutively active version of mDia2 containing formin homology domains 1 and 2 (FH1FH2) and found that they still induced stable MTs and bound to the MT TIP proteins EB1 and APC, which have also been implicated in MT stabilization. A dimerization-impaired mutant of mDia2 (W630A) also generated stable MTs in cells. We examined whether FH1FH2mDia2 had direct activity on MTs in vitro and found that it bound directly to MTs, stabilized MTs against cold- and dilution-induced disassembly, and reduced the rates of growth and shortening during MT assembly and disassembly, respectively. These results indicate that mDia2 has a novel MT stabilization activity that is separate from its actin nucleation activity.
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