Roles for 3' Phosphoinositides in Macropinocytosis.
Roles for 3' Phosphoinositides in Macropinocytosis.
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DOI：
10.1007/978-3-030-94004-1_7
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发表时间：
2022
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大胞饮体形成和成熟的不同运动具有相应的生化活动，这些活动发生在确定的阶段序列和这些阶段之间的过渡中。该过程中的每个阶段都受到磷脂酰肌醇（PtdIns）的各种磷酸化衍生物的调节，这些衍生物位于膜脂质双层的细胞质表面。在肌醇部分的3'位置磷酸化的PtdIns衍生物，称为3'磷酸肌醇（3 'PI），调节序列的不同阶段。3 'PI由许多磷酸肌醇3'-激酶（PI 3 K）和其它脂质激酶和磷酸酶合成，其本身由Ras超家族的小GTP酶调节。这些酶的联合作用将4种主要的3 'PI定位于质膜的不同结构域或离散的细胞器，具有局限于这些结构域的不同生化活性。磷脂酰肌醇（3，4，5）-三磷酸（PtdIns（3，4，5）P3）和磷脂酰肌醇（3，4）-二磷酸（PtdIns（3，4）P2）调节巨胞饮体形成的早期阶段，其包括细胞表面褶皱和闭合成巨胞饮体的环形褶皱的收缩。磷脂酰肌醇3-磷酸（PtdIns 3 P）调节巨胞饮体与其他巨胞饮体和早期内吞细胞器的融合。磷脂酰肌醇（3，5）-二磷酸（PtdIns（3，5）P2）介导大胞饮体成熟和收缩，通过离子和水的损失，以及随后的运输到溶酶体。不同细胞类型中巨胞饮作用的不同特征速率指示调节水平，其可能受细胞产生3 'PI的能力支配。
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 principle 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)P3) and phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2) 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)P2) 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.