Vicenistatin induces early endosome-derived vacuole formation in mammalian cells-猫眼课题宝

DOI：

10.1080/09168451.2015.1132152

发表时间：

2016-02

期刊：

Bioscience, Biotechnology, and Biochemistry

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Yuko Nishiyama;Tomohiro Ohmichi;Sayaka Kazami;H. Iwasaki;Kousuke Mano;Y. Nagumo;F. Kudo;S. Ichikawa;Y. Iwabuchi;N. Kanoh;T. Eguchi;H. Osada;T. Usui

早期内体的同型融合对于有效的蛋白质运输和分选是重要的。这个过程的关键控制器是Rab 5，它调节几种效应物和PtdInsPs水平，但其机制在很大程度上是未知的。在这里，我们报告说，维西他汀，一种天然产物，增强同型融合的早期内涵体，并诱导形成大的空泡状结构在哺乳动物细胞。与另一种早期内体空泡化化合物YM 201636不同，维西他汀在体外不抑制PIKfyve活性，但在细胞中激活Rab 5-PAS途径。此外，维西他汀在体外增加了含胆固醇脂质体的膜表面流动性，并且从质膜剥夺胆固醇刺激了维西他汀诱导的细胞空泡化。这些结果表明，vicenistatin是一种新的化合物，通过激活Rab 5-PAS途径和增加膜流动性诱导空泡样结构的形成。Vicenistatin是一种新型化合物，通过激活Rab 5-PAS通路，增加膜流动性，诱导空泡样结构的形成。

Homotypic fusion of early endosomes is important for efficient protein trafficking and sorting. The key controller of this process is Rab5 which regulates several effectors and PtdInsPs levels, but whose mechanisms are largely unknown. Here, we report that vicenistatin, a natural product, enhanced homotypic fusion of early endosomes and induced the formation of large vacuole-like structures in mammalian cells. Unlike YM201636, another early endosome vacuolating compound, vicenistatin did not inhibit PIKfyve activity in vitro but activated Rab5-PAS pathway in cells. Furthermore, vicenistatin increased the membrane surface fluidity of cholesterol-containing liposomes in vitro, and cholesterol deprivation from the plasma membrane stimulated vicenistatin-induced vacuolation in cells. These results suggest that vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity. Graphical abstract Vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.

Vicenistatin induces early endosome-derived vacuole formation in mammalian cells

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