Uses and abuses of macropinocytosis
Uses and abuses of macropinocytosis
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DOI：
10.1242/jcs.176149
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发表时间：
2016-07-15
影响因子：
4
通讯作者：
Kay, Robert R.
中科院分区：
文献类型：
--
作者：
Bloomfield, Gareth;Kay, Robert R.
巨噬细胞吞噬是真核细胞摄取胞外液和溶解分子的一种方式。它在可以呈现变形虫形态的细胞中被广泛保守，因此，似乎是一种古老的特征，可以追溯到进化的早期阶段。最近的进展突显了这种内吞过程如何在病理过程中被颠覆--某些癌细胞利用巨噬细胞吞噬来摄取细胞外蛋白，许多病毒和细菌利用它进入宿主细胞。Pron和类Pron蛋白也可以通过巨噬细胞吞噬在细胞间传播和繁殖。在治疗上使用巨噬细胞吞噬作用正在取得进展，要么将药物输送到细胞内，要么通过诱导灾难性的快速液体摄取来导致细胞死亡。从机制上讲，RAS信号通路在阿米巴和哺乳动物中起着显著和保守的激活作用；突变的RAS活性异常高的阿米巴类似于肿瘤细胞，它们利用巨噬细胞吞噬所摄取的营养物质提高了生长能力。这篇评论从功能和进化的角度强调了对巨噬细胞吞噬作用的理解和使用的进展，巨噬细胞吞噬作用是单细胞吞噬细胞使用的一种古老的摄食过程，现在已被后生动物细胞用于各种用途，并在疾病状态下被滥用，包括感染和癌症。
Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules. It is widely conserved amongst cells that can take on amoeboid form and, therefore, appears to be an ancient feature that can be traced back to an early stage of evolution. Recent advances have highlighted how this endocytic process can be subverted during pathology - certain cancer cells use macropinocytosis to feed on extracellular protein, and many viruses and bacteria use it to enter host cells. Prion and prion-like proteins can also spread and propagate from cell to cell through macropinocytosis. Progress is being made towards using macropinocytosis therapeutically, either to deliver drugs to or cause cell death by inducing catastrophically rapid fluid uptake. Mechanistically, the Ras signalling pathway plays a prominent and conserved activating role in amoebae and in mammals; mutant amoebae with abnormally high Ras activity resemble tumour cells in their increased capacity for growth using nutrients ingested through macropinocytosis. This Commentary takes a functional and evolutionary perspective to highlight progress in understanding and use of macropinocytosis, which is an ancient feeding process used by single-celled phagotrophs that has now been put to varied uses by metazoan cells and is abused in disease states, including infection and cancer.