Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, Netherlands.
Hubrecht Institute of the Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, Netherlands
J Cell Biol. 2018 Jul 2;217(7):2261-2271. doi: 10.1083/jcb.201802003. Epub 2018 Apr 18.
As a major anabolic pathway, the secretory pathway needs to adapt to the demands of the surrounding environment and responds to different exogenous signals and stimuli. In this context, the transport in the early secretory pathway from the endoplasmic reticulum (ER) to the Golgi apparatus appears particularly regulated. For instance, protein export from the ER is critically stimulated by growth factors. Conversely, nutrient starvation also modulates functions of the early secretory pathway in multiple ways. In this review, we focus on amino-acid starvation and how the function of the early secretory pathway is redirected to fuel autophagy, how the ER exit sites are remodeled into novel cytoprotective stress assemblies, and how secretion is modulated in vivo in starving organisms. With the increasingly exciting knowledge on mechanistic target of rapamycin complex 1 (mTORC1), the major nutrient sensor, it is also a good moment to establish how the modulation of the secretory pathway by amino-acid restriction intersects with this major signaling hub.
作为一个主要的合成代谢途径,分泌途径需要适应周围环境的需求,并对不同的外源信号和刺激做出反应。在这种情况下,从内质网(ER)到高尔基体的早期分泌途径的运输显得特别受调节。例如,生长因子可以显著刺激 ER 中的蛋白质输出。相反,营养饥饿也以多种方式调节早期分泌途径的功能。在这篇综述中,我们重点关注氨基酸饥饿以及早期分泌途径的功能如何被重新定向以促进自噬,内质网出口如何被重塑成新的细胞保护应激组装,以及在饥饿的生物体中如何在体内调节分泌。随着对雷帕霉素复合物 1(mTORC1)这一主要营养传感器的作用机制的认识不断深入,现在也是一个很好的时机来确定氨基酸限制对分泌途径的调节与这一主要信号枢纽之间的相互作用。