Molecular Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
Electron Microscopy Core Facility (EMCF), European Molecular Biology Laboratory, Heidelberg, Germany.
Nat Cell Biol. 2020 Feb;22(2):159-166. doi: 10.1038/s41556-019-0459-2. Epub 2020 Feb 6.
Nuclear pore complexes (NPCs) are very large proteinaceous assemblies that consist of more than 500 individual proteins. NPCs are essential for nucleocytoplasmic transport of different cellular components, and disruption of the integrity of NPCs has been linked to aging, cancer and neurodegenerative diseases. However, the mechanism by which membrane-embedded NPCs are turned over is currently unknown. Here we show that, after nitrogen starvation or genetic interference with the architecture of NPCs, nucleoporins are rapidly degraded in the budding yeast Saccharomyces cerevisiae. We demonstrate that NPC turnover involves vacuolar proteases and the core autophagy machinery. Autophagic degradation is mediated by the cytoplasmically exposed Nup159, which serves as intrinsic cargo receptor and directly binds to the autophagy marker protein Atg8. Autophagic degradation of NPCs is therefore inducible, enabling the removal of individual NPCs from the nuclear envelope.
核孔复合体（NPCs）是由超过 500 个单独蛋白质组成的非常大的蛋白复合物。NPCs 对于不同细胞成分的核质转运是必不可少的，而 NPCs 的完整性被破坏与衰老、癌症和神经退行性疾病有关。然而，目前尚不清楚嵌入膜中的 NPCs 是如何被替换的。在这里，我们发现，在氮饥饿或遗传干扰 NPC 结构后，芽殖酵母酿酒酵母中的核孔蛋白迅速降解。我们证明 NPC 的周转涉及液泡蛋白酶和核心自噬机制。自噬降解由细胞质暴露的 Nup159 介导，它作为内在货物受体并直接与自噬标记蛋白 Atg8 结合。因此，NPC 的自噬降解是可诱导的，能够从核膜中去除单个 NPC。
