The asymmetric segregation of damaged proteins is stem cell-type dependent
The asymmetric segregation of damaged proteins is stem cell-type dependent
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DOI：
10.1083/jcb.201207052
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发表时间：
2013-05-13
影响因子：
7.8
通讯作者：
van der Kooy, Derek
中科院分区：
文献类型：
--
作者：
Bufalino, Mary Rose;DeVeale, Brian;van der Kooy, Derek
在酵母和细菌中，有丝分裂过程中受损蛋白质(DPS)的对称分离与保护细胞免受衰老有关。最近的证据表明，干细胞可能使用类似的机制；然而，到目前为止，还没有体内证据表明在健康的成人干细胞中存在这种效应。我们报道了幼虫(神经母细胞)和成虫(雌性生殖系和肠道干细胞)中的干细胞不对称地分离DPS，例如具有难以降解和年龄相关的2，4-羟基壬烯醛(HNE)修饰的蛋白质。令人惊讶的是，在被分析的细胞中，只有肠道干细胞通过分离HNE到分化的后代来保护自己，而神经母细胞和生殖系干细胞在分裂期间保留HNE。这导致我们认为，决定细胞分裂期间DPS数量的是按时间顺序排列的寿命，而不是细胞类型。此外，我们揭示了非对称DP分裂的生态位依赖和独立机制的作用。
A symmetric segregation of damaged proteins (DPs) during mitosis has been linked in yeast and bacteria to the protection of one cell from aging. Recent evidence suggests that stem cells may use a similar mechanism; however, to date there is no in vivo evidence demonstrating this effect in healthy adult stem cells. We report that stem cells in larval (neuroblast) and adult (female germline and intestinal stem cell) Drosophila melanogaster asymmetrically segregate DPs, such as proteins with the difficult-to-degrade and age-associated 2,4-hydroxynonenal (HNE) modification. Surprisingly, of the cells analyzed only the intestinal stem cell protects itself by segregating HNE to differentiating progeny, whereas the neuroblast and germline stem cells retain HNE during division. This led us to suggest that chronological life span, and not cell type, determines the amount of DPs a cell receives during division. Furthermore, we reveal a role for both niche-dependent and -independent mechanisms of asymmetric DP division.