Mechanistic insights into the anchorage of the contractile ring by anillin and Mid1.

Mechanistic insights into the anchorage of the contractile ring by anillin and Mid1.
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DOI:
10.1016/j.devcel.2015.03.003
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发表时间:
2015-05-26
期刊:
影响因子:
11.8
通讯作者:
Chen, Zhucheng
Chen, Zhucheng
中科院分区:
生物学1区
文献类型:
--
作者:
Sun, Lingfei;Guan, Ruifang;Lee, I-Ju;Liu, Yajun;Chen, Mengran;Wang, Jiawei;Wu, Jian-Qiu;Chen, Zhucheng

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Anillins 和 Mid1 是支架蛋白,分别在动物和真菌胞质分裂期间细胞赤道处收缩环的锚定中发挥关键作用。在这里,我们报告了人苯胺和粟酒裂殖酵母 Mid1 的晶体结构和功能分析。综合数据显示 anillin 包含一个神秘的 C2 结构域和一个 Rho 结合结构域。与束缚 PH 结构域一起,三个膜相关元件协同结合 RhoA 和磷脂,将苯胺固定在裂解沟处。令人惊讶的是,Mid1 还通过一个神秘的 C2 结构域与膜结合。 Mid1 的二聚化导致对 PI(4,5)P2 的高亲和力和偏好,从而将 Mid1 稳定地锚定在分裂平面上,从而绕过了 Rho GTPase 的要求。这些发现揭示了从酵母到人类,通过 anillin/Mid1 家族蛋白进行收缩环锚定的意想不到的通用机制和不同的调节逻辑。
Anillins and Mid1 are scaffold proteins that play key roles in anchorage of the contractile ring at the cell equator during cytokinesis in animals and fungi, respectively. Here, we report crystal structures and functional analysis of human anillin and S. pombe Mid1. The combined data show anillin contains a cryptic C2 domain and a Rho-binding domain. Together with the tethering PH domain, three membrane-associating elements synergistically bind to RhoA and phospholipids to anchor anillin at the cleavage furrow. Surprisingly, Mid1 also binds to the membrane through a cryptic C2 domain. Dimerization of Mid1 leads to high affinity and preference for PI(4,5)P2, which stably anchors Mid1 at the division plane, bypassing the requirement for Rho GTPase. These findings uncover the unexpected general machinery and the divergent regulatory logics for the anchorage of the contractile ring through the anillin/Mid1 family proteins from yeast to humans.
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