Conserved Pib2 regions have distinct roles in TORC1 regulation at the vacuole.
Conserved Pib2 regions have distinct roles in TORC1 regulation at the vacuole.
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DOI：
10.1242/jcs.259994
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发表时间：
2022-09-15
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
TORC 1是真核生物细胞生长的关键控制因子。在酵母（酿酒酵母）中，营养物质的存在通过几个上游调节传感器向TORC 1发出信号，这些传感器共同协调TORC 1活性。TORC 1定位于液泡膜和内体膜，在那里发生差异信号。这种定位是模仿Pib 2，一个关键的上游TORC 1调节器，是必不可少的营养饥饿或药理学抑制后TORC 1重新激活。Pib 2对TORC 1活性有积极和消极的影响，但其机制仍然知之甚少。在这里，我们查明Pib 2抑制功能TORC 1的短，保守的N-末端区域内的残基。我们还表明，Pib 2的C-末端区域，螺旋区E和尾巴，是必不可少的TORC 1的重新激活。此外，Pib 2 FYVE结构域在液泡定位中起作用，但令人惊讶的是，它对于从雷帕霉素暴露中恢复是不必要的。使用嵌合Pib 2靶向结构，我们表明，内体定位是没有必要的TORC 1重新激活和雷帕霉素治疗后的细胞生长。因此，Pib 2的全面分子解剖表明，其每个保守区域差异有助于Pib 2介导的TORC 1活性调节。概述：S.酿酒酵母Pib 2是一种关键的TORC 1调节因子，通过保守区域抑制和激活TORC 1活性，是雷帕霉素暴露后恢复和细胞生长的关键。
TORC1 is a critical controller of cell growth in eukaryotes. In yeast (Saccharomyces cerevisiae), the presence of nutrients is signaled to TORC1 by several upstream regulatory sensors that together coordinate TORC1 activity. TORC1 localizes to both vacuolar and endosomal membranes, where differential signaling occurs. This localization is mimicked by Pib2, a key upstream TORC1 regulator that is essential for TORC1 reactivation after nutrient starvation or pharmacological inhibition. Pib2 has both positive and negative effects on TORC1 activity, but the mechanisms remain poorly understood. Here, we pinpoint the Pib2 inhibitory function on TORC1 to residues within short, conserved N-terminal regions. We also show that the Pib2 C-terminal regions, helical region E and tail, are essential for TORC1 reactivation. Furthermore, the Pib2 FYVE domain plays a role in vacuolar localization, but it is surprisingly unnecessary for recovery from rapamycin exposure. Using chimeric Pib2 targeting constructs, we show that endosomal localization is not necessary for TORC1 reactivation and cell growth after rapamycin treatment. Thus, a comprehensive molecular dissection of Pib2 demonstrates that each of its conserved regions differentially contribute to Pib2-mediated regulation of TORC1 activity. Summary: Vacuolar localization of S. cerevisiae Pib2, a key TORC1 regulator that both inhibits and activates TORC1 activity via conserved regions, is key for recovery and cell growth following rapamycin exposure.
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影响因子：
16
作者：
Dubouloz, F;Deloche, O;De Virgillo, C
通讯作者：
De Virgillo, C
影响因子：
64.8
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通讯作者：
Hassabis D
影响因子：
14.9
作者：
Dubreuil B;Sass E;Nadav Y;Heidenreich M;Georgeson JM;Weill U;Duan Y;Meurer M;Schuldiner M;Knop M;Levy ED
通讯作者：
Levy ED
影响因子：
16
作者：
Binda, Matteo;Peli-Gulli, Marie-Pierre;De Virgilio, Claudio
通讯作者：
De Virgilio, Claudio
DOI：
10.1073/pnas.1701030114
发表时间：
2017-06-06
影响因子：
11.1
作者：
Jeong, Hanbin;Park, Jumi;Lee, Changwook
通讯作者：
Lee, Changwook