Macropinocytosis: Biology and mechanisms
Macropinocytosis: Biology and mechanisms
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DOI：
10.1016/j.cdev.2021.203713
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发表时间：
2021-12-01
影响因子：
3.9
通讯作者：
Kay, Robert R.
中科院分区：
文献类型：
--
作者：
Kay, Robert R.
巨胞饮作用是通过质膜的皱褶和杯状结构进行的一种内吞作用。这些接近于将培养基液滴捕获到微米大小的囊泡中，这些囊泡通过内吞系统运输，其内容物被消化并且有用的产物被吸收。巨胞饮作用在某些免疫细胞中是组成性的，并且在许多其他细胞中由生长因子刺激。它发生在动物王国和变形虫中，暗示着一个深刻的进化历史。它的科学历史可以追溯到100年前，但越来越多的工作集中在它在免疫系统，癌细胞喂养，以及作为病毒和药物进入细胞的后门中的医学重要性。巨胞饮是由肌动蛋白细胞骨架驱动的，其动力学可以通过晶格光片显微镜来了解：这揭示了形成巨胞饮体的多种途径。在网骨藻中，巨胞饮杯在质膜中围绕PIP3和活性Ras和Rac的结构域组织。它们将Arp 2/3复合物的激活剂吸引到它们的外围，形成肌动蛋白聚合环，从而形成杯状结构。PIP3结构域的大小由RasGAP（如NF 1）和脂质磷酸酶PTEN控制。这是可能的域动力学决定的形状，演变和大胞饮结构的关闭。
Macropinocytosis is a form of endocytosis performed by ruffles and cups of the plasma membrane. These close to entrap droplets of medium into micron-sized vesicles, which are trafficked through the endocytic system, their contents digested and useful products absorbed. Macropinocytosis is constitutive in certain immune cells and stimulated in many other cells by growth factors. It occurs across the animal kingdom and in amoebae, implying a deep evolutionary history. Its scientific history goes back 100 years, but increasingly work is focused on its medical importance in the immune system, cancer cell feeding, and as a backdoor into cells for viruses and drugs. Macropinocytosis is driven by the actin cytoskeleton whose dynamics can be appreciated with lattice light sheet microscopy: this reveals a surprising variety of routes for forming macropinosomes. In Dictyostelium amoebae, macropinocytic cups are organized around domains of PIP3 and active Ras and Rac in the plasma membrane. These attract activators of the Arp2/3 complex to their periphery, creating rings of actin polymerization that shape the cups. The size of PIP3 domains is controlled by RasGAPs, such as NF1, and the lipid phosphatase, PTEN. It is likely that domain dynamics determine the shape, evolution and closing of macropinocytic structures.