PTRN-1/CAMSAP promotes CYK-1/formin-dependent actin polymerization during endocytic recycling
PTRN-1/CAMSAP promotes CYK-1/formin-dependent actin polymerization during endocytic recycling
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PTRN-1/CAMSAP 在内吞循环过程中促进 CYK-1/formin 依赖性肌动蛋白聚合
DOI：
10.15252/embj.201798556
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发表时间：
2018-05-02
期刊：
影响因子：
11.4
通讯作者：
Shi, Anbing
中科院分区：
文献类型：
--
作者：
Gong, Ting;Yan, Yanling;Shi, Anbing
货物分类和膜载体启动回收核内体需要适当协调的肌动蛋白动力学。然而，在循环运输过程中肌动蛋白组织调节的机制仍然是难以捉摸的。在这里，我们报道PTRN-1/CAMSAP的缺失阻碍了肌动蛋白交换并减少了胞质肌动蛋白结构。此外，我们发现PTRN-1是回收不依赖网格蛋白的货物hTAC-GFP所必需的。PTRN-1的n端钙钙蛋白同源结构域（CH）和中心线圈区（CC）可以协同维持hTAC-GFP的流动。我们发现CYK-1/formin是PTRN-1的结合伙伴。CYK-1的n端GTPase-binding domain （GBD）是PTRN-1 CH domain的结合接口。PTRN-1 CH结构域的存在促进了CYK-1介导的肌动蛋白聚合，这表明PTRN-1-CH:CYK-1- gbd相互作用有效地缓解了CYK-1内部的自抑制相互作用。正如预期的那样，在ptrn-1突变体中，CYK-1双formin同源结构域2 （FH2）的过表达大大恢复了肌动蛋白结构，并部分抑制了hTAC-GFP过积累表型。我们得出结论，PTRN-1 CH结构域需要刺激CYK-1以促进内吞循环过程中的肌动蛋白动力学。
Cargo sorting and membrane carrier initiation in recycling endosomes require appropriately coordinated actin dynamics. However, the mechanism underlying the regulation of actin organization during recycling transport remains elusive. Here we report that the loss of PTRN-1/CAMSAP stalled actin exchange and diminished the cytosolic actin structures. Furthermore, we found that PTRN-1 is required for the recycling of clathrin-independent cargo hTAC-GFP. The N-terminal calponin homology (CH) domain and central coiled-coils (CC) region of PTRN-1 can synergistically sustain the flow of hTAC-GFP. We identified CYK-1/formin as a binding partner of PTRN-1. The N-terminal GTPase-binding domain (GBD) of CYK-1 serves as the binding interface for the PTRN-1 CH domain. The presence of the PTRN-1 CH domain promoted CYK-1-mediated actin polymerization, which suggests that the PTRN-1-CH:CYK-1-GBD interaction efficiently relieves autoinhibitory interactions within CYK-1. As expected, the overexpression of the CYK-1 formin homology domain 2 (FH2) substantially restored actin structures and partially suppressed the hTAC-GFP overaccumulation phenotype in ptrn-1 mutants. We conclude that the PTRN-1 CH domain is required to stimulate CYK-1 to facilitate actin dynamics during endocytic recycling.