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首页> 外文期刊>PLoS Biology >Spire and Formin 2 Synergize and Antagonize in Regulating Actin Assembly in Meiosis by a Ping-Pong Mechanism
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Spire and Formin 2 Synergize and Antagonize in Regulating Actin Assembly in Meiosis by a Ping-Pong Mechanism

机译：Spire和Formin 2通过乒乓机制协同和拮抗减数分裂中肌动蛋白的组装。

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In mammalian oocytes, three actin binding proteins, Formin 2 (Fmn2), Spire, and profilin, synergistically organize a dynamic cytoplasmic actin meshwork that mediates translocation of the spindle toward the cortex and is required for successful fertilization. Here we characterize Fmn2 and elucidate the molecular mechanism for this synergy, using bulk solution and individual filament kinetic measurements of actin assembly dynamics. We show that by capping filament barbed ends, Spire recruits Fmn2 and facilitates its association with barbed ends, followed by rapid processive assembly and release of Spire. In the presence of actin, profilin, Spire, and Fmn2, filaments display alternating phases of rapid processive assembly and arrested growth, driven by a “ping-pong” mechanism, in which Spire and Fmn2 alternately kick off each other from the barbed ends. The results are validated by the effects of injection of Spire, Fmn2, and their interacting moieties in mouse oocytes. This original mechanism of regulation of a Rho-GTPase–independent formin, recruited by Spire at Rab11a-positive vesicles, supports a model for modulation of a dynamic actin-vesicle meshwork in the oocyte at the origin of asymmetric positioning of the meiotic spindle.
机译：在哺乳动物卵母细胞中，三种肌动蛋白结合蛋白，即Formin 2（Fmn2），Spire和profilin协同组织了动态的细胞质肌动蛋白网，介导纺锤体向皮层的移位，是成功受精所必需的。在这里，我们表征Fmn2，并阐明了这种协同作用的分子机制，使用了体积溶液和肌动蛋白组装动力学的单个细丝动力学测量。我们显示，通过覆盖细丝倒刺末端，Spire募集了Fmn2并促进其与倒刺末端的关联，然后快速进行组装和释放Spire。在存在肌动蛋白，蛋白纤溶酶，Spire和Fmn2的情况下，细丝表现出快速进行性组装和停滞生长的交替阶段，这是由“乒乓”机制驱动的，在该机制中，Spire和Fmn2从带刺的末端交替开始。通过在小鼠卵母细胞中注射Spire，Fmn2及其相互作用部分的效果验证了该结果。 Spire在Rab11a阳性囊泡处招募的这种独立于Rho-GTPase的福尔明的原始调节机制，为减数分裂纺锤体不对称定位起源的卵母细胞中动态肌动蛋白-囊泡网的调节模型提供了支持。

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