Single-molecule imaging of a three-component ordered actin disassembly mechanism.

Single-molecule imaging of a three-component ordered actin disassembly mechanism.
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DOI:
10.1038/ncomms8202
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发表时间:
2015-05-21
影响因子:
16.6
通讯作者:
Goode, Bruce L.
Goode, Bruce L.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Jansen, Silvia;Collins, Agnieszka;Chin, Samantha M.;Ydenberg, Casey A.;Gelles, Jeff;Goode, Bruce L.

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细胞破坏和快速分解丝状肌动蛋白网络的机制仍然难以捉摸;然而,Coronin、Cofilin和AIP1参与了这一过程。通过多波长单分子荧光成像,我们发现哺乳动物Cor1B、Cof1和AIP1通过一个时间有序的途径协同作用,诱导肌动蛋白丝的高效切断和分解。Cor1B首先结合到纤维上,并显著加速随后Cof1的结合,导致大量修饰和稳定的纤维。Cof1反过来招募AIP1,后者迅速触发切断并保持与新产生的带刺末端的结合。在这三种蛋白质的存在下,由切断产生的倒刺末端的新生长被特异性地阻断。这种活性使我们能够重建并直接看到单个肌动蛋白丝被形成蛋白在其带刺末端快速聚合,同时沿着其长度随机切断和封顶,并从其尖端拆卸。Coronin, Cofilin和AIP1在促进肌动蛋白分解中的作用尚未得到很好的理解。Jansen等人利用单分子荧光成像技术表明,这三种蛋白在一个协调的时间途径中共同作用,诱导肌动蛋白细丝的快速切断和拆卸。
The mechanisms by which cells destabilize and rapidly disassemble filamentous actin networks have remained elusive; however, Coronin, Cofilin and AIP1 have been implicated in this process. Here using multi-wavelength single-molecule fluorescence imaging, we show that mammalian Cor1B, Cof1 and AIP1 work in concert through a temporally ordered pathway to induce highly efficient severing and disassembly of actin filaments. Cor1B binds to filaments first, and dramatically accelerates the subsequent binding of Cof1, leading to heavily decorated, stabilized filaments. Cof1 in turn recruits AIP1, which rapidly triggers severing and remains bound to the newly generated barbed ends. New growth at barbed ends generated by severing was blocked specifically in the presence of all three proteins. This activity enabled us to reconstitute and directly visualize single actin filaments being rapidly polymerized by formins at their barbed ends while simultanteously being stochastically severed and capped along their lengths, and disassembled from their pointed ends. The roles of Coronin, Cofilin and AIP1 in promoting actin disassembly have not been well understood. Here using single-molecule fluorescence imaging, Jansen et al. show that the three proteins act together in a coordinated, temporal pathway to induce rapid severing and disassembly of actin filaments.
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