Cordon-bleu is an actin nucleation factor and controls neuronal morphology

Cordon-bleu is an actin nucleation factor and controls neuronal morphology
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DOI:
10.1016/j.cell.2007.08.030
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发表时间:
2007-10-19
期刊:
影响因子:
64.5
通讯作者:
Qualmann, Britta
Qualmann, Britta
中科院分区:
生物学1区
文献类型:
--
作者:
Ahuja, Rashmi;Pinyol, Roser;Qualmann, Britta

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尽管形成了丰富的不同的肌动蛋白结构,但只有两种肌动蛋白成核因子在脊椎动物中得到了很好的确定:Arp2/3复合物和形成蛋白。在这里,我们描述了另一种成核剂,蓝带成核剂(Cobl)。Cobl是一种脑富集蛋白,使用三个Wiskott-Aldrich综合征蛋白同源2 (WH2)结构域与肌动蛋白结合。球茎促进不捆绑,不分枝的花丝。细丝的形成依赖于倒钩端生长,需要所有三个Cobl WH2结构域和扩展连接子L2。我们认为Cobl的成核能力是基于三个肌动蛋白单体在交叉丝取向上的组装。Cobl定位于肌动蛋白高动态位点并调节细胞形态。在神经元中,Cobl的表达作用极大地增加了神经突和神经突分支的诱导,而Cobl的表达作用主要依赖于Cobl的肌动蛋白成核能力。相应地,钴的消耗导致树枝状乔木化减少。因此,Cobl是控制神经元形态和发育的肌动蛋白成核因子。
Despite the wealth of different actin structures formed, only two actin nucleation factors are well established in vertebrates: the Arp2/3 complex and formins. Here, we describe a further nucleator, cordon-bleu (Cobl). Cobl is a brainenriched protein using three Wiskott-Aldrich syndrome protein homology 2 (WH2) domains for actin binding. Cobl promotes nonbundled, unbranched filaments. Filament formation relies on barbed-end growth and requires all three Cobl WH2 domains and the extended linker L2. We suggest that the nucleation power of Cobl is based on the assembly of three actin monomers in cross-filament orientation. Cobl localizes to sites of high actin dynamics and modulates cell morphology. In neurons, induction of both neurites and neurite branching is dramatically increased by Cobl expression effects that critically depend on Cobl's actin nucleation ability. Correspondingly, Cobl depletion results in decreased dendritic arborization. Thus, Cobl is an actin nucleator controlling neuronal morphology and development.