Paoletti Camille, Quintin Sophie, Matifas Audrey, Charvin Gilles
Development and Stem Cells Department, IGBMC, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France.
Development and Stem Cells Department, IGBMC, CNRS UMR 7104, INSERM U964, Université de Strasbourg, Illkirch, France.
Biophys J. 2016 Apr 12;110(7):1605-1614. doi: 10.1016/j.bpj.2016.02.034.
Budding yeast cells have a finite replicative life span; that is, a mother cell produces only a limited number of daughter cells before it slows division and dies. Despite the gradual aging of the mother cell, all daughters are born rejuvenated and enjoy a full replicative lifespan. It has been proposed that entry of mother cells into senescence is driven by the progressive accumulation and retention of damaged material, including protein aggregates. This additionally allows the daughter cells to be born damage free. However, the mechanism underlying such asymmetrical segregation of protein aggregates by mother and daughter cells remains controversial, in part because of the difficulties inherent in tracking the dynamics and fate of protein aggregates in vivo. To overcome such limitations, we have developed single-cell real-time imaging methodology to track the formation of heat-induced protein aggregates in otherwise unperturbed dividing cells. By combining the imaging data with a simple computational model of protein aggregation, we show that the establishment of asymmetrical partitioning of protein aggregates upon division is driven by the large bud-specific dilution rate associated with polarized growth and the absence of significant mother/bud exchange of protein aggregates during the budded phase of the cell cycle. To our knowledge, this study sheds new light on the mechanism of establishment of a segregation bias, which can be accounted for by simple physical arguments.
出芽酵母细胞具有有限的复制寿命；也就是说，母细胞在减缓分裂并死亡之前只能产生有限数量的子细胞。尽管母细胞会逐渐衰老，但所有子细胞在诞生时都是新生的，并享有完整的复制寿命。有人提出，母细胞进入衰老状态是由包括蛋白质聚集体在内的受损物质的逐渐积累和滞留所驱动的。这也使得子细胞在诞生时没有损伤。然而，母细胞和子细胞对蛋白质聚集体进行这种不对称分离的机制仍存在争议，部分原因是在体内追踪蛋白质聚集体的动态和命运存在固有的困难。为了克服这些限制，我们开发了单细胞实时成像方法，以追踪在其他方面未受干扰的分裂细胞中热诱导蛋白质聚集体的形成。通过将成像数据与蛋白质聚集的简单计算模型相结合，我们表明，细胞分裂时蛋白质聚集体不对称分配的建立是由与极化生长相关的大芽特异性稀释率以及细胞周期芽生阶段蛋白质聚集体在母细胞/芽之间没有显著交换所驱动的。据我们所知，这项研究为分离偏差建立的机制提供了新的见解，这可以通过简单的物理论证来解释。
