PDF(Pubmed)
Abstract：
Eukaryotic cells have developed intricate mechanisms for biomolecule transport, particularly in stressful conditions. This interdisciplinary study delves into unconventional protein secretion (UPS) pathways activated during starvation, facilitating the export of proteins bypassing most of the components of the classical secretory machinery. Specifically, we focus on the underexplored mechanisms of the GRASP\'s role in UPS, particularly in biogenesis and cargo recruitment for the vesicular-like compartment for UPS. Our results show that liquid-liquid phase separation (LLPS) plays a key role in the coacervation of Grh1, the GRASP yeast homologue, under starvation-like conditions. This association seems a precursor to the Compartment for Unconventional Protein Secretion (CUPS) biogenesis. Grh1\'s self-association is regulated by electrostatic, hydrophobic, and hydrogen-bonding interactions. Importantly, our study demonstrates that phase-separated states of Grh1 can recruit UPS cargo under starvation-like situations. Additionally, we explore how the coacervate liquid-to-solid transition could impact cells\' ability to return to normal post-stress states. Our findings offer insights into intracellular protein dynamics and cell adaptive responses to stress.
摘要：
真核细胞已经开发了复杂的生物分子转运机制，特别是在紧张的条件下。这项跨学科研究深入研究了饥饿期间激活的非常规蛋白质分泌（UPS）途径，促进蛋白质的出口，绕过经典分泌机制的大多数组件。具体来说,我们专注于GRASP在UPS中的作用未得到充分开发的机制，特别是在UPS的囊泡状隔室的生物发生和货物募集中。我们的结果表明，液-液相分离（LLPS）在GRASP酵母同源物Grh1的凝聚中起着关键作用，在类似饥饿的条件下。这种关联似乎是非常规蛋白质分泌（CUPS）生物发生隔室的前兆。Grh1的自缔合是由静电调节的，疏水，和氢键相互作用。重要的是,我们的研究表明，在类似饥饿的情况下，Grh1的相分离状态可以招募UPS货物。此外,我们探讨了凝聚层液-固转变如何影响细胞恢复正常应激后状态的能力。我们的发现提供了对细胞内蛋白质动力学和细胞对压力的适应性反应的见解。
