Egami Youhei
Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa, 761-0793, Japan.
Anat Sci Int. 2016 Jan;91(1):35-42. doi: 10.1007/s12565-015-0313-y. Epub 2015 Nov 3.
Phagocytosis and macropinocytosis, actin-dependent endocytic pathways that mediate the uptake of particles and fluid, respectively, are fundamental routes that enable cells to sample their environment, eliminate pathogens and endogenous cell debris, and contribute to immunoprotection and the maintenance of tissue homeostasis. These processes require a well-organized network of actin cytoskeletal remodeling and membrane transport, which are spatiotemporally regulated by small GTPases. The Rab family of small GTPases, which functions as molecular switches, plays central roles in intracellular membrane trafficking. Although multiple Rab proteins are localized to phagosomes and regulate phagosome maturation, the precise role of each Rab family member in Fcγ receptor (FcγR)-mediated phagocytosis is not fully characterized. Recently, we revealed that Rab35 and Rab20 are important regulators of phagosome formation and maturation, respectively. This review summarizes the functional implication of these Rab GTPases during FcγR-mediated phagocytosis in macrophages. Currently, compared with our knowledge of the regulatory mechanisms of receptor-mediated endocytosis including phagocytosis, the molecular components and signaling cascades of macropinocytosis remain poorly elucidated. Our time-lapse imaging showed that several Rab GTPases are sequentially recruited to the membrane of macropinosomes. Based on our observations, these findings regarding the spatiotemporal localization of Rab GTPases during macropinocytosis are introduced.
吞噬作用和巨胞饮作用分别是介导颗粒和液体摄取的肌动蛋白依赖性内吞途径，是细胞感知周围环境、清除病原体和内源性细胞碎片、以及促进免疫保护和维持组织稳态的基本途径。这些过程需要一个由肌动蛋白细胞骨架重塑和膜转运组成的组织良好的网络，而这一网络受到小GTP酶的时空调节。作为分子开关发挥作用的小GTP酶Rab家族，在细胞内膜运输中起着核心作用。尽管多种Rab蛋白定位于吞噬体并调节吞噬体成熟，但每个Rab家族成员在Fcγ受体（FcγR）介导的吞噬作用中的精确作用尚未完全明确。最近，我们发现Rab35和Rab20分别是吞噬体形成和成熟的重要调节因子。本综述总结了这些Rab GTP酶在巨噬细胞FcγR介导的吞噬作用中的功能意义。目前，与我们对包括吞噬作用在内的受体介导的内吞作用调节机制的了解相比，巨胞饮作用的分子成分和信号级联仍未得到充分阐明。我们的延时成像显示，几种Rab GTP酶被依次招募到大胞饮体的膜上。基于我们的观察结果，本文介绍了关于Rab GTP酶在巨胞饮作用期间的时空定位的这些发现。
