Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa, Japan.
Subcell Biochem. 2022;98:119-141. doi: 10.1007/978-3-030-94004-1_7.
The distinct movements of macropinosome formation and maturation have corresponding biochemical activities which occur in a defined sequence of stages and transitions between those stages. Each stage in the process is regulated by variously phosphorylated derivatives of phosphatidylinositol (PtdIns) which reside in the cytoplasmic face of the membrane lipid bilayer. PtdIns derivatives phosphorylated at the 3' position of the inositol moiety, called 3' phosphoinositides (3'PIs), regulate different stages of the sequence. 3'PIs are synthesized by numerous phosphoinositide 3'-kinases (PI3K) and other lipid kinases and phosphatases, which are themselves regulated by small GTPases of the Ras superfamily. The combined actions of these enzymes localize four principal species of 3'PI to distinct domains of the plasma membrane or to discrete organelles, with distinct biochemical activities confined to those domains. Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P) and phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P) regulate the early stages of macropinosome formation, which include cell surface ruffling and constrictions of circular ruffles which close into macropinosomes. Phosphatidylinositol 3-phosphate (PtdIns3P) regulates macropinosome fusion with other macropinosomes and early endocytic organelles. Phosphatidylinositol (3,5)-bisphosphate (PtdIns(3,5)P) mediates macropinosome maturation and shrinkage, through loss of ions and water, and subsequent traffic to lysosomes. The different characteristic rates of macropinocytosis in different cell types indicate levels of regulation which may be governed by the cell's capacity to generate 3'PIs.
大胞饮泡的形成和成熟有独特的运动，这些运动具有相应的生化活性，它们按照特定的阶段顺序和阶段之间的转变发生。该过程的每个阶段都受到膜脂双层细胞质面中各种不同磷酸化形式的磷脂酰肌醇（PtdIns）的调节。在肌醇部分的 3'位置被磷酸化的 PtdIns 衍生物，称为 3'磷酸肌醇（3'PIs），调节该序列的不同阶段。3'PIs 由许多磷酸肌醇 3-激酶（PI3K）和其他脂质激酶和磷酸酶合成，这些酶本身又受到 Ras 超家族的小 GTPase 的调节。这些酶的共同作用将四种主要的 3'PI 定位到质膜的不同区域或离散的细胞器，将具有不同生化活性的物质局限在这些区域。磷脂酰肌醇（3,4,5）-三磷酸（PtdIns（3,4,5）P）和磷脂酰肌醇（3,4）-二磷酸（PtdIns（3,4）P）调节大胞饮泡形成的早期阶段，包括细胞表面起皱和环状皱襞的收缩，这些环状皱襞收缩形成大胞饮泡。磷脂酰肌醇 3-磷酸（PtdIns3P）调节大胞饮泡与其他大胞饮泡和早期内吞细胞器的融合。磷脂酰肌醇（3,5）-二磷酸（PtdIns（3,5）P）通过离子和水的丧失以及随后向溶酶体的运输，介导大胞饮泡的成熟和收缩。不同细胞类型中大胞饮作用的不同特征速率表明，这种调节可能受到细胞生成 3'PIs 的能力的控制。
