Mechanistic aspects of mammalian cell size control
Mechanistic aspects of mammalian cell size control
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DOI：
10.1111/dgd.12334
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发表时间：
2017-01
期刊：
影响因子：
4.6
通讯作者：
Kazuo Yamamoto;T. Mak
中科院分区：
文献类型：
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作者：
Kazuo Yamamoto;T. Mak
一组分化细胞的大小分布往往在一个恒定的范围内。然而，体外和体内研究表明，细胞可以暂时改变它们的大小，以响应它们周围的环境和它们受到的刺激。因此，必须有一种机制，通常保持单元格大小恒定，同时允许在必要时切换到另一个大小。为了研究哺乳动物细胞大小控制的分子基础，我们在人类T细胞系中进行了遗传筛选，以确定参与细胞大小调节的基因。从这个筛选中出现的主要候选者当它过表达时增加细胞大小，但当受到siRNA敲低时减少细胞大小。一些证据表明，该基因的产物，我们称之为“Largen”，以一种与mRNA特定子集上调相关的方式调节mRNA翻译，其中许多影响线粒体功能。事实上，过表达Largen的细胞增加了线粒体的质量和活性，增加了ATP的产生。这些体外观察结果已经在体内用转基因小鼠模型复制。针对这些发现，我们讨论了线粒体对哺乳动物细胞大小控制的可能贡献。
Size distribution in a group of differentiated cells often falls into a constant range. However, in vitro and in vivo studies have shown that cells can temporarily change their size in response to their surrounding environment and the stimuli they receive. Thus, there must be a mechanism that normally keeps cell size constant while allowing a shift to an alternative size when necessary. To investigate the molecular basis of mammalian cell size control, we conducted a genetic screen in a human T cell line to identify genes involved in cell size regulation. A prime candidate emerging from this screen increases cell size when it is overexpressed but reduces cell size when subjected to siRNA knockdown. Several lines of evidence indicate that the product of this gene, which we called “Largen”, regulates mRNA translation in a manner associated with the upregulation of a specific subset of mRNAs, many of which affect mitochondrial function. In fact, cells overexpressing Largen increase both mitochondrial mass and activity, enhancing ATP production. These in vitro observations have been replicated in vivo using transgenic mouse models. With a focus on these findings, we discuss the possible contribution of mitochondria to the control of mammalian cell size.