Buckley Catherine M, King Jason S
Department of Biomedical Sciences, Centre for Membrane Interactions and Dynamics, University of Sheffield, UK.
Bateson Centre, University of Sheffield, UK.
FEBS J. 2017 Nov;284(22):3778-3790. doi: 10.1111/febs.14115. Epub 2017 Jun 5.
Macropinocytosis is a mechanism for the nonspecific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment, extract extracellular nutrients and regulate plasma membrane turnover. Macropinocytosis has recently been implicated in several diseases including cancer, neurodegenerative diseases and atherosclerosis. Uptake by macropinocytosis is also exploited by several intracellular pathogens to gain entry into host cells. Both capturing and subsequently processing large volumes of extracellular fluid poses a number of unique challenges for the cell. Macropinosome formation requires coordinated three-dimensional manipulation of the cytoskeleton to form shaped protrusions able to entrap extracellular fluid. The following maturation of these large vesicles then involves a complex series of membrane rearrangements to shrink and concentrate their contents, while delivering components required for digestion and recycling. Recognition of the diverse importance of macropinocytosis in physiology and disease has prompted a number of recent studies. In this article, we summarise advances in our understanding of both macropinosome formation and maturation, and seek to highlight the important unanswered questions.
巨吞饮作用是一种非特异性大量摄取和内化细胞外液的机制。通过允许细胞对其环境进行采样、摄取细胞外营养物质并调节质膜周转，它在巨噬细胞、树突状细胞和神经元等多种细胞类型中发挥着特定且独特的作用。巨吞饮作用最近被认为与包括癌症、神经退行性疾病和动脉粥样硬化在内的多种疾病有关。几种细胞内病原体也利用巨吞饮作用摄取来进入宿主细胞。捕获并随后处理大量细胞外液给细胞带来了许多独特的挑战。巨吞饮体的形成需要对细胞骨架进行协调的三维操纵，以形成能够捕获细胞外液的成形突起。这些大囊泡随后的成熟涉及一系列复杂的膜重排，以收缩并浓缩其内容物，同时输送消化和循环所需的成分。对巨吞饮作用在生理学和疾病中不同重要性的认识促使了最近的一些研究。在本文中，我们总结了对巨吞饮体形成和成熟理解的进展，并试图突出重要的未解决问题。
