Engulfment of the midbody remnant after cytokinesis in mammalian cells
Engulfment of the midbody remnant after cytokinesis in mammalian cells
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DOI：
10.1242/jcs.154732
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发表时间：
2014-09-01
影响因子：
4
通讯作者：
Echard, Arnaud
中科院分区：
文献类型：
--
作者：
Crowell, Elizabeth Faris;Gaffuri, Anne-Lise;Echard, Arnaud
细胞运动脱落后产生的中体残留物最近引起了人们的广泛关注，因为它可能对哺乳动物细胞的细胞分化和肿瘤发生有至关重要的影响。据报道，在这些细胞中，MBR要么被释放到细胞外介质中，要么被收回到两个子细胞中的一个细胞中，在那里它可以通过自噬被降解。在这里，我们描述了在人类和小鼠的各种永生化细胞、癌细胞和原代干细胞中的主要替代途径。利用相关的光学显微镜、扫描电子显微镜和定量分析，我们发现中体两侧的连续脱落产生了游离的MBR，这些MBR通过依赖于钙/镁的受体与细胞表面紧密联系。令人惊讶的是，MBR在细胞表面移动了几个小时，最终被一种依赖于肌动蛋白的吞噬类机制吞噬。数学模型结合实验进一步证明，溶酶体的活动完全解释了MBR被吞噬后的清除。这项研究改变了我们对MBR在哺乳动物细胞中如何遗传和降解的理解，并提出了一种MBR在细胞间长距离传递信号的机制。
The midbody remnant (MBR) that is generated after cytokinetic abscission has recently attracted a lot of attention, because it might have crucial consequences for cell differentiation and tumorigenesis in mammalian cells. In these cells, it has been reported that the MBR is either released into the extracellular medium or retracted into one of the two daughter cells where it can be degraded by autophagy. Here, we describe a major alternative pathway in a variety of human and mouse immortalized cells, cancer cells and primary stem cells. Using correlative light and scanning electron microscopy and quantitative assays, we found that sequential abscissions on both sides of the midbody generate free MBRs, which are tightly associated with the cell surface through a Ca2+/Mg2+-dependent receptor. Surprisingly, MBRs move over the cell surface for several hours, before being eventually engulfed by an actin-dependent phagocytosis-like mechanism. Mathematical modeling combined with experimentation further demonstrates that lysosomal activities fully account for the clearance of MBRs after engulfment. This study changes our understanding of how MBRs are inherited and degraded in mammalian cells and suggests a mechanism by which MBRs might signal over long distances between cells.