MRC-Laboratory of Molecular Biology , Francis Crick Avenue, Cambridge CB2 0QH , UK.
Philos Trans R Soc Lond B Biol Sci. 2019 Feb 4;374(1765):20180150. doi: 10.1098/rstb.2018.0150.
Macropinocytosis-the large-scale, non-specific uptake of fluid by cells-is used by Dictyostelium discoideum amoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing. It is accepted that PIP3 is required for efficient macropinocytosis. Here, we assess the roles of Ras and Rac in Dictyostelium macropinocytosis. Gain-of-function experiments show that macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved. Among the activating guanine exchange factors (GEFs), GefF is implicated in macropinocytosis by an insertional mutant. The individual roles of Rho family proteins are little understood but activation of at least some may be independent of PIP3. This article is part of the Theo Murphy meeting issue 'Macropinocytosis'.
大胞饮作用——细胞大规模、非特异性地摄取液体——被粘菌细胞（Dictyostelium discoideum amoebae）用来获取营养。这些细胞在由一小片磷酸肌醇（3,4,5）-三磷酸（PIP3）和已激活的 Ras 和 Rac 小 G 蛋白组成的膜区域周围形成环状皱襞。当这个皱襞关闭时，一小部分培养基被包裹到细胞内部进行进一步处理。人们普遍认为 PIP3 是有效大胞饮作用所必需的。在这里，我们评估了 Ras 和 Rac 在粘菌大胞饮作用中的作用。功能获得实验表明，持续的 Ras 激活刺激大胞饮作用，遗传分析表明 RasG 和 RasS 是涉及的关键 Ras 蛋白。在激活的鸟苷交换因子（GEFs）中，GefF 通过插入突变体与大胞饮作用有关。Rho 家族蛋白的个体作用知之甚少，但至少有一些的激活可能与 PIP3 无关。本文是主题为“大胞饮作用”的 Theo Murphy 会议文章的一部分。
