WTS-1/LATS regulates endocytic recycling by restraining F-actin assembly in a synergistic manner
WTS-1/LATS regulates endocytic recycling by restraining F-actin assembly in a synergistic manner
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WTS-1/LATS 通过以协同方式抑制 F-肌动蛋白组装来调节内吞再循环。
DOI：
10.1242/jcs.259085
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发表时间：
2021
影响因子：
4
通讯作者：
Shi Anbing
中科院分区：
文献类型：
--
作者：
Zhang Hanchong;Cheng Zihang;Li Wenbo;Hu Jie;Zhao Linyue;Chen Dan;Gao Jinghu;Chen Juan;Yan Yanling;Lin Long;Shi Anbing
内体肌动蛋白结构的破坏对内吞循环产生负面影响。然而，在循环过程中调节肌动蛋白组织的潜在稳态机制仍不清楚。在本研究中，我们确定了秀丽隐杆线虫内体肌动蛋白组装的协同限制机制，涉及WTS-1/LATS激酶，该激酶是Hippo通路的核心成分。WTS-1位于分选核内体上，与肌动蛋白聚合调节因子PTRN-1/CAMSAPs共定位。我们在WTS-1缺陷细胞中观察到PTRN-1标记结构的增加，表明WTS-1可以限制PTRN-1的内体定位。因此，wts -1缺失细胞中的肌动蛋白过度积累表型被相关的PTRN-1缺失所减轻。我们进一步证明，wts -1缺陷细胞中的再循环缺陷和肌动蛋白过度积累通过过表达组成活性的UNC-60A/cofilin（S3A）而减少，这与LATS作为cofilin活性的正调节因子的作用一致。总之，我们的数据证实了之前的发现，我们提出了一个额外的模型：WTS-1与UNC-60A/cofilin介导的肌动蛋白分解一起作用，通过抑制PTRN-1驻留在内体上，限制内体f -肌动蛋白的组装，从而保持再循环运输。
The disruption of endosomal actin architecture negatively affects endocytic recycling. However, the underlying homeostatic mechanisms that regulate actin organization during recycling remain unclear. In this study, we identified a synergistic endosomal actin assembly restricting mechanism in C. elegans involving WTS-1/LATS kinase, which is a core component of the Hippo pathway. WTS-1 resides on the sorting endosomes and colocalizes with the actin polymerization regulator PTRN-1/CAMSAPs. We observed an increase in PTRN-1-labeled structures in WTS-1-deficient cells, indicating that WTS-1 can limit the endosomal localization of PTRN-1. Accordingly, the actin overaccumulation phenotype in WTS-1-depleted cells was mitigated by the associated PTRN-1 loss. We further demonstrated that recycling defects and actin overaccumulation in WTS-1-deficient cells were reduced by the overexpression of constitutively active UNC-60A/cofilin(S3A), which aligns with the role of LATS as a positive regulator of cofilin activity. Altogether, our data confirmed previous findings, and we proposed an additional model: WTS-1 acts alongside the UNC-60A/cofilin-mediated actin disassembly to restrict the assembly of endosomal F-actin by curbing PTRN-1 dwelling on endosomes, preserving recycling transport.