TOR 复合物 1 是 Rho1 GTPase 的直接靶标。
The TOR complex 1 is a direct target of Rho1 GTPase.
机构信息
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
出版信息
Mol Cell. 2012 Mar 30;45(6):743-53. doi: 10.1016/j.molcel.2012.01.028. Epub 2012 Mar 22.
Abstract
The TOR complex 1 (TORC1) in yeast is regulated by various stress conditions. However, the underlying mechanism is poorly understood. In this study, we show that stresses affect TORC1 function through Rho1, a member of Rho family GTPases. Upon activation by stresses, Rho1 binds directly to Kog1, a unique component of TORC1, resulting in downregulation of TORC1 activity and disruption of its membrane association. The binding also triggers the release and activation of the Tap42-2A phosphatase, a major effector of TORC1 that resides on the complex. Rapamycin and caffeine also induce Rho1 activation. While the two agents inhibit TOR directly, their effects on TORC1 signaling are largely dependent on Rho1 activation. Our findings demonstrate that TORC1 acts both upstream and downstream of Rho1 GTPase, unveiling a mechanism that integrates stress and nutrient signals to coordinate Rho1-mediated spatial expansion and TORC1-dependent mass increase.
摘要
酵母中的 TOR 复合物 1（TORC1）受各种应激条件的调节。然而，其潜在机制尚不清楚。在本研究中，我们表明应激通过 Rho1（Rho 家族 GTPases 的一员）影响 TORC1 的功能。在受到应激激活后，Rho1 直接与 Kog1（TORC1 的独特组成部分）结合，导致 TORC1 活性下调和其膜结合破坏。这种结合还触发了 Tap42-2A 磷酸酶的释放和激活，该磷酸酶是位于复合物上的 TORC1 的主要效应物。雷帕霉素和咖啡因也诱导 Rho1 的激活。虽然这两种药物直接抑制 TOR，但它们对 TORC1 信号的影响在很大程度上取决于 Rho1 的激活。我们的研究结果表明，TORC1 既在上游又在 Rho1 GTPase 下游起作用，揭示了一种整合应激和营养信号的机制，以协调 Rho1 介导的空间扩展和 TORC1 依赖性质量增加。
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