雷帕霉素靶蛋白（Rheb）-TORC1 信号轴作为发育检查点发挥作用。
The Rheb-TORC1 signaling axis functions as a developmental checkpoint.
机构信息
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University, Houston, TX 77030, USA.
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Texas A&M University, Houston, TX 77030, USA
出版信息
Development. 2020 Mar 2;147(5):dev181727. doi: 10.1242/dev.181727.
In many eukaryotes, the small GTPase Rheb functions as a switch to toggle activity of TOR complex 1 (TORC1) between anabolism and catabolism, thus controlling lifespan, development and autophagy. Our CRISPR-generated, fluorescently tagged endogenous RHEB-1 and DAF-15/Raptor are expressed ubiquitously and localize to lysosomes. LET-363/TOR and DAF-15/Raptor are required for development beyond the third larval stage (L3). We observed that deletion of RHEB-1 similarly conferred L3 arrest. Unexpectedly, robust RNAi-mediated depletion of TORC1 components caused arrest at stages prior to L3. Accordingly, conditional depletion of endogenous DAF-15/Raptor in the soma revealed that TORC1 is required at each stage of the life cycle to progress to the next stage. Reversal of DAF-15 depletion permits arrested animals to recover to continue development. Our results are consistent with TORC1 functioning as a developmental checkpoint that governs the decision of the animal to progress through development.
在许多真核生物中，小分子 GTP 酶 Rheb 作为一个开关，在合成代谢和分解代谢之间调节 TOR 复合物 1（TORC1）的活性，从而控制寿命、发育和自噬。我们通过 CRISPR 产生的、荧光标记的内源性 RHEB-1 和 DAF-15/Raptor 广泛表达，并定位于溶酶体。LET-363/TOR 和 DAF-15/Raptor 对于第三龄幼虫（L3）之后的发育是必需的。我们观察到，RHEB-1 的缺失同样导致 L3 停滞。出乎意料的是，强烈的 RNAi 介导的 TORC1 成分耗竭导致 L3 之前的阶段停滞。因此，在体细胞中条件性耗尽内源性 DAF-15/Raptor 表明 TORC1 在生命周期的每个阶段都需要前进到下一个阶段。DAF-15 耗竭的逆转允许被阻止的动物恢复继续发育。我们的结果与 TORC1 作为发育检查点的功能一致，该检查点控制动物通过发育的决策。
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