Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Department of Science, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Biochem Biophys Res Commun. 2021 Apr 23;550:158-165. doi: 10.1016/j.bbrc.2021.02.141. Epub 2021 Mar 9.
Chromosomes have their own territories and dynamically translocate in response to internal and external cues. However, whether and how territories and the relocation of chromosomes are controlled by other intracellular organelles remains unknown. Upon nutrient starvation and target of rapamycin complex 1 (TORC1) inactivation, micronucleophagy, which preferentially degrades nucleolar proteins, occurs at the nucleus-vacuole junction (NVJ) in budding yeast. Ribosomal DNA (rDNA) is condensed and relocated against the NVJ, whereas nucleolar proteins move towards the NVJ for micronucleophagic degradation, causing dissociation of nucleolar proteins from rDNA. These findings imply that the NVJ is the critical platform in the directional movements of rDNA and nucleolar proteins. Here, we show that cells lacking the NVJ (NVJΔ cells) largely lost rDNA condensation and rDNA-nucleolar protein separation after TORC1 inactivation. The macronucleophagy receptor Atg39, an outer nuclear membrane protein, accumulated at the NVJ and was degraded by micronucleophagy. These suggested that macronucleophagy is also dependent on the presence of the NVJ. However, micronucleophagy, but not macronucleophagy, was abolished in NVJΔ cells. This study clearly demonstrated that vacuoles controls intranuclear events, nucleolar dynamics, from outside of the nucleus via the NVJ under the control of TORC1.
染色体拥有自己的领地,并能根据内部和外部信号动态地进行易位。然而,其他细胞内细胞器是否以及如何控制领地和染色体的重定位仍然未知。在营养饥饿和雷帕霉素靶蛋白复合体 1(TORC1)失活时,微核自噬(micronucleophagy)会优先降解核仁蛋白,发生在出芽酵母的核-液泡连接点(NVJ)。核糖体 DNA(rDNA)浓缩并重新定位到 NVJ,而核仁蛋白向 NVJ 移动进行微核自噬降解,导致核仁蛋白与 rDNA 分离。这些发现表明,NVJ 是 rDNA 和核仁蛋白定向运动的关键平台。在这里,我们表明,缺乏 NVJ(NVJΔ 细胞)的细胞在 TORC1 失活后,rDNA 浓缩和 rDNA-核仁蛋白分离的现象大大减少。外核膜蛋白 Atg39 作为巨核自噬受体,积累在 NVJ 处,并被微核自噬降解。这表明巨核自噬也依赖于 NVJ 的存在。然而,在 NVJΔ 细胞中,仅微核自噬,而不是巨核自噬,被消除。这项研究清楚地表明,液泡通过 NVJ 从细胞核外部控制核内事件和核仁动态,这一过程受 TORC1 的调控。