Up-regulation of the Cdc42 GTPase limits the replicative life span of budding yeast.
Up-regulation of the Cdc42 GTPase limits the replicative life span of budding yeast.
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DOI：
10.1091/mbc.e21-04-0208
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发表时间：
2022-04-01
影响因子：
3.3
通讯作者：
Park, Hay-Oak
中科院分区：
文献类型：
--
作者：
Kang, Pil Jung;Mullner, Rachel;Li, Haoyu;Hansford, Derek;Shen, Han-Wei;Park, Hay-Oak
Cdc42是一种保守的Rho GT3，在酵母和动物的极性建立中起着核心作用。细胞极性是细胞不对称分裂的关键，而不对称细胞分裂是芽殖酵母复制老化的基础。然而，Cdc42和其他极性因素如何影响寿命在很大程度上是未知的。在这里，我们通过活细胞成像显示，在重复的细胞分裂过程中，野生型中活性Cdc42水平偶尔升高，但在长寿的bud8缺失细胞中很少。我们发现了一个新的Bud8定位与胞质分裂残余物，这也招募Rga1，Cdc42 GTdR激活蛋白。遗传分析和活细胞成像表明，Rga 1和Bud8可能通过调节活性Cdc42水平而对寿命产生相反的影响。rga 1突变体寿命较短，在极性建立缺陷的未出芽状态下死亡。值得注意的是，Cdc42在老细胞中积累，其轻度过表达加速衰老，伴随频繁的对称细胞分裂，尽管对年轻细胞没有有害影响。我们的研究结果暗示，这些积极和消极的极性因素之间的相互作用限制了芽殖酵母的寿命。
Cdc42, a conserved Rho GTPase, plays a central role in polarity establishment in yeast and animals. Cell polarity is critical for asymmetric cell division, and asymmetric cell division underlies replicative aging of budding yeast. Yet how Cdc42 and other polarity factors impact life span is largely unknown. Here we show by live-cell imaging that the active Cdc42 level is sporadically elevated in wild type during repeated cell divisions but rarely in the long-lived bud8 deletion cells. We find a novel Bud8 localization with cytokinesis remnants, which also recruit Rga1, a Cdc42 GTPase activating protein. Genetic analyses and live-cell imaging suggest that Rga1 and Bud8 oppositely impact life span likely by modulating active Cdc42 levels. An rga1 mutant, which has a shorter life span, dies at the unbudded state with a defect in polarity establishment. Remarkably, Cdc42 accumulates in old cells, and its mild overexpression accelerates aging with frequent symmetric cell divisions, despite no harmful effects on young cells. Our findings implicate that the interplay among these positive and negative polarity factors limits the life span of budding yeast.