Eps8 controls actin-based motility by capping the barbed ends of actin filaments
Eps8 controls actin-based motility by capping the barbed ends of actin filaments
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DOI：
10.1038/ncb1199
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发表时间：
2004-12-01
影响因子：
21.3
通讯作者：
Scita, G
中科院分区：
文献类型：
--
作者：
Disanza, A;Carlier, MF;Scita, G
肌动蛋白丝带刺端盖蛋白对细胞运动至关重要，因为它们调节肌动蛋白丝的生长以产生推进力。一种封盖蛋白家族，其原型是凝胶蛋白，具有模块化结构、作用机制和通过信号依赖机制（如Ca2+或磷脂酰肌醇-4,5-磷酸结合）进行调节。在这里，我们发现另一个家族的蛋白质，Eps8家族，也显示出倒钩末端封盖活性，这位于其保守的羧基末端效应域。Eps8的孤立效应域覆盖了具有纳米摩尔亲和力的倒钩末端。相反，全长Eps8在体外被自我抑制，与Abi1蛋白的相互作用减轻了这种抑制。在体内，Eps8被招募到肌动蛋白动态位点，它的移除损害了肌动蛋白的推进。eps8家族蛋白与凝胶样蛋白没有任何相似性。因此，我们的研究结果确定了一个新的肌动蛋白帽盖家族，并揭示了通过蛋白质-蛋白质相互作用调节帽盖的新模式。Eps8 - Abi1复合体的一个已确定的功能是参与小GTPase Rac的激活，这表明该复合体在肌动蛋白动力学中具有多方面的作用，可能通过参与其他更大的复合体。
Actin filament barbed-end capping proteins are essential for cell motility, as they regulate the growth of actin filaments to generate propulsive force. One family of capping proteins, whose prototype is gelsolin, shares modular architecture, mechanism of action, and regulation through signalling-dependent mechanisms, such as Ca2+ or phosphatidylinositol-4,5- phosphate binding. Here we show that proteins of another family, the Eps8 family, also show barbed- end capping activity, which resides in their conserved carboxy-terminal effector domain. The isolated effector domain of Eps8 caps barbed ends with an affinity in the nanomolar range. Conversely, full-length Eps8 is auto-inhibited in vitro, and interaction with the Abi1 protein relieves this inhibition. In vivo, Eps8 is recruited to actin dynamic sites, and its removal impairs actin-based propulsion. Eps8-family proteins do not show any similarity to gelsolin-like proteins. Thus, our results identify a new family of actin cappers, and unveil novel modalities of regulation of capping through protein - protein interactions. One established function of the Eps8 - Abi1 complex is to participate in the activation of the small GTPase Rac, suggesting a multifaceted role for this complex in actin dynamics, possibly through the participation in alternative larger complexes.