MRC Laboratory of Molecular Biology, Cambridge, UK.
Department of Computer Science, University of Warwick, Coventry, UK.
Subcell Biochem. 2022;98:41-59. doi: 10.1007/978-3-030-94004-1_3.
Macropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in the endo-lysosomal system. They use macropinocytosis for feeding, maintaining a high rate of fluid uptake that makes assay and experimentation easy. Mutants collected over the years identify cytoskeletal and signalling proteins required for macropinocytosis. Cups are organized around plasma membrane domains of intense PIP3, Ras and Rac signalling, proper formation of which also depends on the RasGAPs NF1 and RGBARG, PTEN, the PIP3-regulated protein kinases Akt and SGK and their activators PDK1 and TORC2, Rho proteins, plus other components yet to be identified. This PIP3 domain directs dendritic actin polymerization to the extending lip of macropinocytic cups by recruiting a ring of the SCAR/WAVE complex around itself and thus activating the Arp2/3 complex. The dynamics of PIP3 domains are proposed to shape macropinocytic cups from start to finish. The role of the Ras-PI3-kinase module in organizing feeding structures in unicellular organisms most likely predates its adoption into growth factor signalling, suggesting an evolutionary origin for growth factor signalling.
巨胞饮作用是一种相对未被探索的大规模胞吞作用形式，由肌动蛋白细胞骨架驱动。粘菌变形虫从细胞膜延伸的杯中形成巨胞饮体，然后消化其内容物并吸收内体溶酶体系统中的营养物质。它们利用巨胞饮作用来进食，保持高的液体摄取率，这使得检测和实验变得容易。多年来收集的突变体鉴定了巨胞饮作用所需的细胞骨架和信号蛋白。杯状结构围绕着富含 PIP3、Ras 和 Rac 信号的质膜域组织，其正确形成还依赖于 RasGAPs NF1 和 RGBARG、PTEN、受 PIP3 调节的蛋白激酶 Akt 和 SGK 及其激活剂 PDK1 和 TORC2、Rho 蛋白以及其他尚未确定的成分。这个 PIP3 结构域通过将 SCAR/WAVE 复合物的一个环自身周围募集，从而将树突状肌动蛋白聚合到巨胞饮杯中延伸的边缘，从而激活 Arp2/3 复合物。PIP3 结构域的动力学被认为从一开始就塑造了巨胞饮杯的形状。 Ras-PI3-激酶模块在组织单细胞生物中的进食结构中的作用很可能先于其被纳入生长因子信号转导，这表明生长因子信号转导具有进化起源。
