Self-organization of Plk4 regulates symmetry breaking in centriole duplication
Self-organization of Plk4 regulates symmetry breaking in centriole duplication
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DOI：
10.1038/s41467-019-09847-x
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发表时间：
2019-04-18
影响因子：
16.6
通讯作者：
Kitagawa, Daiju
中科院分区：
文献类型：
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作者：
Yamamoto, Shohei;Kitagawa, Daiju
在中心粒复制过程中，母中心粒旁边形成了一个单一的女儿中心粒。决定单个复制位点的分子机制仍然是一个长期存在的问题。在这里，我们表明Plk4的内在自组织与中心粒复制过程中的对称性破坏有关。我们证明了Plk4有能力通过内在的无序连接体将其相分离成凝聚体，并且Plk4的缩合性质受自身磷酸化的调节。一直以来，中心粒Plk4的解离动力学都是由自身磷酸化控制的。我们进一步发现，在原中心醇形成开始之前，自磷酸化的Plk4已经作为单个焦点分布在母中心粒周围，并随后被靶向STIL-HsSAS6负载。Plk4自组织的扰动影响中心粒Plk4分布的不对称性和适当的中心粒复制。总之，我们认为Plk4的空间模式的形成是每个母中心粒一个重复位点的决定因素。
During centriole duplication, a single daughter centriole is formed next to the mother centriole. The molecular mechanism that determines a single duplication site remains a long-standing question. Here, we show that intrinsic self-organization of Plk4 is implicated in symmetry breaking in the process of centriole duplication. We demonstrate that Plk4 has an ability to phase-separate into condensates via an intrinsically disordered linker and that the condensation properties of Plk4 are regulated by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophosphorylated Plk4 is already distributed as a single focus around the mother centriole before the initiation of procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbation of Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and proper centriole duplication. Overall, we propose that the spatial pattern formation of Plk4 is a determinant of a single duplication site per mother centriole.