Species-Specific Functions of Twinfilin in Actin Filament Depolymerization.
Species-Specific Functions of Twinfilin in Actin Filament Depolymerization.
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DOI：
10.1016/j.jmb.2018.06.025
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发表时间：
2018-09-14
影响因子：
5.6
通讯作者：
Goode BL
中科院分区：
文献类型：
--
作者：
Hilton DM;Aguilar RM;Johnston AB;Goode BL
Twinfilin 是肌动蛋白解聚因子同源 (ADF-H) 蛋白超家族的高度保守成员，该家族还包括 ADF/Cofilin、Abp1/Drebrin、GMF 和 Coactosin。 Twinfilin 具有独特的分子结构，由两个 ADF-H 结构域组成，两个 ADF-H 结构域通过连接子连接，后面是 C 末端尾部。 Yeast Twinfilin 与酵母环化酶相关蛋白 (Srv2/CAP) 结合，可提高肌动蛋白丝的倒刺末端和尖端的解聚速率。然而，目前尚不清楚这些活性是否扩展到其他物种的 Twinfilin 同源物。为了解决这个问题，我们纯化了三种小鼠 Twinfilin 亚型（mTwf1、mTwf2a、mTwf2b）和小鼠 CAP1，并使用 TIRF 显微镜检测来研究它们对细丝分解的影响。我们的结果表明，所有三种小鼠 Twinfilin 亚型都加速了与酵母 Twinfilin 相似的倒刺末端解聚，表明这种活性在进化上是保守的。与此形成鲜明对比的是，小鼠 Twinfilin 亚型和 CAP1 未能诱导快速的尖端解聚。使用嵌合体，我们表明酵母特异性的尖端解聚活性是由酵母 Twinfilin 的 C 端 ADF-H 结构域指定的。此外，原肌球蛋白对丝的修饰未能阻止酵母和小鼠 Twinfilin 和 Srv2/CAP 的解聚，但抑制了 Cofilin 的断裂。总之，我们的结果表明，Twinfilin 在调节倒刺末端动力学方面具有保守功能，尽管其驱动快速尖端解聚的能力似乎具有物种特异性。我们讨论了这项工作的意义，包括不同物种中不同 ADF-H 家族成员可能催化尖端解聚。
Twinfilin is a highly conserved member of the actin depolymerization factor homology (ADF-H) protein superfamily, which also includes ADF/Cofilin, Abp1/Drebrin, GMF, and Coactosin. Twinfilin has a unique molecular architecture consisting of two ADF-H domains joined by a linker and followed by a C-terminal tail. Yeast Twinfilin, in conjunction with yeast cyclase-associated protein (Srv2/CAP), increases the rate of depolymerization at both the barbed and pointed ends of actin filaments. However, it has remained unclear whether these activities extend to Twinfilin homologs in other species. To address this, we purified the three mouse Twinfilin isoforms (mTwf1, mTwf2a, mTwf2b) and mouse CAP1, and used TIRF microscopy assays to study their effects on filament disassembly. Our results show that all three mouse Twinfilin isoforms accelerate barbed end depolymerization similar to yeast Twinfilin, suggesting that this activity is evolutionarily conserved. In striking contrast, mouse Twinfilin isoforms and CAP1 failed to induce rapid pointed end depolymerization. Using chimeras, we show that the yeast-specific pointed end depolymerization activity is specified by the C-terminal ADF-H domain of yeast Twinfilin. Additionally, Tropomyosin decoration of filaments failed to impede depolymerization by yeast and mouse Twinfilin and Srv2/CAP, but inhibited Cofilin severing. Together, our results indicate that Twinfilin has conserved functions in regulating barbed end dynamics, although its ability to drive rapid pointed end depolymerization appears to be species-specific. We discuss the implications of this work, including that pointed end depolymerization may be catalyzed by different ADF-H family members in different species.
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影响因子：
7.8
作者：
DREES, B;BROWN, C;BRETSCHER, A
通讯作者：
BRETSCHER, A
影响因子：
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作者：
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通讯作者：
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DOI：
10.1083/jcb.201501094
发表时间：
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期刊：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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