German Cancer Research Center (DKFZ), Heidelberg, Germany.
Subcell Biochem. 2022;98:143-167. doi: 10.1007/978-3-030-94004-1_8.
Macropinocytosis is an evolutionarily conserved endocytic pathway that mediates non-selective uptake of extracellular fluid in bulk. Macropinocytosis is initiated by localized polymerization of the actin cytoskeleton, which generates plasma membrane protrusions that enclose part of the environment into large endocytic vesicles. From amoebae to mammalian cells, the actin dynamics that drive macropinosome formation are regulated by a conserved set of intracellular signaling proteins including Ras superfamily GTPases and PI3-kinases. In mammalian cells, multiple upstream signaling pathways control activity of these core regulators in response to cell-extrinsic and cell-intrinsic stimuli. Growth factor signaling pathways play a central role in macropinocytosis induction. In addition, an increasing number of functionally diverse processes has been identified as macropinocytosis regulators, including several nutrient-sensing and developmental signaling pathways. Many of these signaling pathways have proto-oncogenic properties, and their dysregulation drives the high macropinocytic activity that is commonly observed in cancer cells. These regulatory principles illustrate how macropinocytosis is controlled by complex upstream inputs to exert diverse cellular functions in physiological and pathological contexts.
巨胞饮作用是一种进化上保守的内吞途径，可介导细胞外液的非选择性摄取。巨胞饮作用由肌动蛋白细胞骨架的局部聚合起始，产生质膜突起，将部分环境包围成大的内吞小泡。从变形虫到哺乳动物细胞，驱动巨胞饮体形成的肌动蛋白动力学受到一组保守的细胞内信号蛋白的调节，包括 Ras 超家族 GTP 酶和 PI3-激酶。在哺乳动物细胞中，多种上游信号通路控制这些核心调节剂的活性，以响应细胞外和细胞内刺激。生长因子信号通路在巨胞饮作用的诱导中起核心作用。此外，越来越多的功能多样化的过程已被确定为巨胞饮作用的调节剂，包括几种营养感应和发育信号通路。其中许多信号通路具有原癌基因特性，其失调导致癌细胞中常见的高巨胞饮活性。这些调节原则说明了巨胞饮作用是如何通过复杂的上游输入来控制的，以在生理和病理环境中发挥多种细胞功能。
