Target of rapamycin signaling mediates vacuolar fission caused by endoplasmic reticulum stress in Saccharomyces cerevisiae.
Target of rapamycin signaling mediates vacuolar fission caused by endoplasmic reticulum stress in Saccharomyces cerevisiae.
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DOI：
10.1091/mbc.e15-06-0344
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发表时间：
2015-12-15
影响因子：
3.3
通讯作者：
Powers T
中科院分区：
文献类型：
--
作者：
Stauffer B;Powers T
为了响应内质网（ER）的压力，酵母液泡碎片成更小的囊泡。这一过程独立于已知的ER应激途径，但需要TORC 1及其效应子Sch 9和Tap 42/Sit 4。一个全基因组的视觉屏幕揭示了新的组件，可能与TORC 1相互作用，以调节液泡碎片。酵母液泡相当于哺乳动物的溶酶体，在不同的生理和环境刺激下，其大小和数量都会发生变化。在这里，我们表明，空泡片段在内质网（ER）内的化学或遗传扰动引起的应激反应。我们确定这种反应不涉及先前与ER应激相关的已知信号通路，而是需要雷帕霉素敏感的TOR复合物1（TORC 1），细胞生长的主要调节因子，以及其下游效应子Tap 42/Sit 4和Sch 9。为了确定ER应激诱导的空泡碎片化所需的其他因素，我们进行了高通量，全基因组的视觉筛选酵母突变体是难治性ER应激诱导的空泡形态的变化。我们确定了几个基因先前所需的液泡融合和/或分裂，验证这种方法的实用性。我们还确定了一些新的组件重要的碎片，包括一组蛋白质参与组装的V-ATP酶。值得注意的是，我们发现，其中之一，Vph 2，经历了变化，在细胞内定位响应ER应力，而且，在某种程度上，需要TORC 1活性。总之，这些结果揭示了一个新的作用TORC 1在液泡行为的调节。
In response to endoplasmic reticulum (ER) stress, the yeast vacuole fragments into smaller vesicles. This process is independent of known ER stress pathways but requires TORC1 and its effectors, Sch9 and Tap42/Sit4. A genome-wide visual screen reveals new components that are likely to interact with TORC1 to regulate vacuolar fragmentation. The yeast vacuole is equivalent to the mammalian lysosome and, in response to diverse physiological and environmental stimuli, undergoes alterations both in size and number. Here we demonstrate that vacuoles fragment in response to stress within the endoplasmic reticulum (ER) caused by chemical or genetic perturbations. We establish that this response does not involve known signaling pathways linked previously to ER stress but instead requires the rapamycin-sensitive TOR Complex 1 (TORC1), a master regulator of cell growth, together with its downstream effectors, Tap42/Sit4 and Sch9. To identify additional factors required for ER stress–induced vacuolar fragmentation, we conducted a high-throughput, genome-wide visual screen for yeast mutants that are refractory to ER stress–induced changes in vacuolar morphology. We identified several genes shown previously to be required for vacuolar fusion and/or fission, validating the utility of this approach. We also identified a number of new components important for fragmentation, including a set of proteins involved in assembly of the V-ATPase. Remarkably, we find that one of these, Vph2, undergoes a change in intracellular localization in response to ER stress and, moreover, in a manner that requires TORC1 activity. Together these results reveal a new role for TORC1 in the regulation of vacuolar behavior.