Mechanism of actin capping protein recruitment and turnover during clathrin-mediated endocytosis
Mechanism of actin capping protein recruitment and turnover during clathrin-mediated endocytosis
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DOI：
10.1083/jcb.202306154
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发表时间：
2023-11-15
影响因子：
7.8
通讯作者：
Di Pietro，Santiago M.
中科院分区：
文献类型：
--
作者：
Lamb，Andrew K.;Fernandez，Andres N.;Di Pietro，Santiago M.
网格蛋白介导的内吞作用依赖于支链肌动蛋白网络的聚合，以提供膜内陷的力。肌动蛋白加帽蛋白（actin capping protein，CP）是肌动蛋白分支网络形成的关键调节因子，它与肌动蛋白丝的倒刺末端结合，防止肌动蛋白亚基的增加或丢失。CP被认为是随机结合肌动蛋白丝，但最近的证据表明，CP是由一组含有CP相互作用（CPI）基序的蛋白质调节。重要的是，CPI基序蛋白如何共同发挥作用来调节CP还知之甚少。在这里，我们显示Aim21和Bsp1协同工作，通过它们的CPI基序将CP招募到芽殖酵母中的内吞肌动蛋白网络中，CPI基序也变构地调节加帽强度。相反，twinfilin工程下游的CP招聘，调节营业额的CP通过其CPI基序和非变构机制。总的来说，我们的研究结果揭示了三个CPI基序蛋白如何在胞吞过程中以逐步的方式共同调节CP。
Clathrin-mediated endocytosis depends on polymerization of a branched actin network to provide force for membrane invagination. A key regulator in branched actin network formation is actin capping protein (CP), which binds to the barbed end of actin filaments to prevent the addition or loss of actin subunits. CP was thought to stochastically bind actin filaments, but recent evidence shows CP is regulated by a group of proteins containing CP-interacting (CPI) motifs. Importantly, how CPI motif proteins function together to regulate CP is poorly understood. Here, we show Aim21 and Bsp1 work synergistically to recruit CP to the endocytic actin network in budding yeast through their CPI motifs, which also allosterically modulate capping strength. In contrast, twinfilin works downstream of CP recruitment, regulating the turnover of CP through its CPI motif and a non-allosteric mechanism. Collectively, our findings reveal how three CPI motif proteins work together to regulate CP in a stepwise fashion during endocytosis.