Tilney L G, DeRosier D J, Tilney M S
Department of Biology, University of Pennsylvania, Philadelphia 19104.
J Cell Biol. 1992 Jul;118(1):71-81. doi: 10.1083/jcb.118.1.71.
After Listeria is phagocytosed by a macrophage, it dissolves the phagosomal membrane and enters the cytoplasm. The Listeria then nucleates actin filaments from its surface. These actin filaments rearrange to form a tail with which the Listeria moves to the macrophage surface as a prelude to spreading. Since individual actin filaments appear to remain in their same positions in the tail in vitro after extraction with detergent, the component filaments must be cross-bridged together. From careful examination of the distribution of actin filaments attached to the surface of Listeria and in the tail, and the fact that during and immediately after division filaments are not nucleated from the new wall formed during septation, we show how a cloud of actin filaments becomes rearranged into a tail simply by the mechanics of growth. From lineage studies we can relate the length of the tail to the age of the surface of Listeria and make predictions as to the ratio of Listeria with varying tail lengths at a particular time after the initial infection. Since we know that division occurs about every 50 min, after 4 h we would predict that if we started with one Listeria in a macrophage, 16 bacteria would be found, two with long tails, two with medium tails, four with tiny tails, and eight with no tails or a ratio of 1:1:2:4. We measured the lengths of the tails on Listeria 4 h after infection in serial sections and confirmed this prediction. By decorating the actin filaments that make up the tail of Listeria with subfragment 1 of myosin we find (a) that the filaments are indeed short (maximally 0.3 microns in length); (b) that the filament length is approximately the same at the tip and the base of the tail; and (c) that the polarity of these filaments is inappropriate for myosin to be responsible or to facilitate movement through the cytoplasm, but the polarity insures that the bacterium will be located at the tip of a pseudopod, a location that is essential for spreading to an adjacent cell. Putting all this information together we can begin to unravel the problem of how the Listeria forms the cytoskeleton and what is the biological purpose of this tail. Two functions are apparent: movement and pseudopod formation.
单核细胞增生李斯特菌被巨噬细胞吞噬后,会溶解吞噬体膜并进入细胞质。然后,李斯特菌从其表面使肌动蛋白丝成核。这些肌动蛋白丝重新排列形成一条尾巴,李斯特菌利用这条尾巴移动到巨噬细胞表面,作为扩散的前奏。由于在用去污剂提取后,体外单个肌动蛋白丝似乎在尾巴中保持其相同位置,所以组成丝必须通过交叉桥连在一起。通过仔细检查附着在李斯特菌表面和尾巴中的肌动蛋白丝的分布,以及在分裂期间和刚分裂后丝不是从隔膜形成的新壁上成核这一事实,我们展示了一团肌动蛋白丝如何仅通过生长机制重新排列成一条尾巴。通过谱系研究,我们可以将尾巴的长度与李斯特菌表面的年龄相关联,并预测在初次感染后的特定时间具有不同尾巴长度的李斯特菌的比例。由于我们知道大约每50分钟发生一次分裂,4小时后我们预测,如果我们从巨噬细胞中的一个李斯特菌开始,将会发现16个细菌,两个有长尾巴,两个有中等尾巴,四个有短尾巴,八个没有尾巴,即比例为1:1:2:4。我们在连续切片中测量了感染4小时后李斯特菌尾巴的长度,并证实了这一预测。通过用肌球蛋白的亚片段1修饰构成李斯特菌尾巴的肌动蛋白丝,我们发现:(a)这些丝确实很短(最大长度为0.3微米);(b)尾巴尖端和基部的丝长度大致相同;(c)这些丝的极性不适合肌球蛋白负责或促进在细胞质中移动,但这种极性确保细菌将位于伪足的尖端,这一位置对于扩散到相邻细胞至关重要。综合所有这些信息,我们可以开始解开李斯特菌如何形成细胞骨架以及这条尾巴的生物学目的是什么的问题。有两个功能是显而易见的:移动和伪足形成。