Fazeli Gholamreza, Wehman Ann Marie
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, 97080, Germany.
Biol Cell. 2017 Oct;109(10):355-363. doi: 10.1111/boc.201700028. Epub 2017 Aug 25.
Phagocytosis and autophagy are two distinct pathways that degrade external and internal unwanted particles. Both pathways lead to lysosomal degradation inside the cell, and over the last decade, the line between them has blurred; autophagy proteins were discovered on phagosomes engulfing foreign bacteria, leading to the proposal of LC3-associated phagocytosis (LAP). Many proteins involved in macroautophagy are used for phagosome degradation, although Atg8/LC3 family proteins only decorate the outer membrane of LC3-associated phagosomes, in contrast to both autophagosome membranes. A few proteins distinguish LAP from autophagy, such as components of the autophagy pre-initiation complex. However, most LAP cargo is wrapped in multiple layers of membranes, making them similar in structure to autophagosomes. Recent evidence suggests that LC3 is important for the degradation of internal membranes, explaining why LC3 would be a vital part of both macroautophagy and LAP. In addition to removing invading pathogens, multicellular organisms also use LAP to degrade cell debris, including cell corpses and photoreceptor outer segments. The post-mitotic midbody remnant is another cell fragment, which results from each cell division, that was recently added to the growing list of LAP cargoes. Thus, LAP plays an important role during the normal physiology and homoeostasis of animals.
吞噬作用和自噬作用是两条不同的途径,分别用于降解外部和内部不需要的颗粒。这两条途径都会导致细胞内的溶酶体降解,在过去十年间,它们之间的界限变得模糊;人们在吞噬外来细菌的吞噬体上发现了自噬蛋白,从而提出了LC3相关吞噬作用(LAP)。许多参与巨自噬的蛋白质被用于吞噬体降解,不过与自噬体的双层膜不同,Atg8/LC3家族蛋白仅附着在LC3相关吞噬体的外膜上。有一些蛋白质可将LAP与自噬区分开来,比如自噬起始前复合体的组分。然而,大多数LAP的货物都被多层膜包裹,这使得它们在结构上与自噬体相似。最近的证据表明,LC3对于内膜的降解很重要,这就解释了为什么LC3会成为巨自噬和LAP的重要组成部分。除了清除入侵的病原体,多细胞生物还利用LAP来降解细胞碎片,包括细胞尸体和光感受器外段。有丝分裂后的中间体残余物是另一种细胞碎片,它产生于每次细胞分裂,最近也被列入了越来越多的LAP货物清单中。因此,LAP在动物的正常生理和体内平衡过程中发挥着重要作用。