Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast Saccharomyces cerevisiae, NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited. Yeast cells treated with azetidine-2-carboxylic acid, a proline analog that induces protein misfolding, display the most dramatic increase in NEB, suggesting a causal link to protein quality control. This link was further supported by both localization of ubiquitin and Hsp104 to protein aggregates and NEB events, and the evolution of these structures during heat shock. We hypothesize that NEB is part of normal cellular physiology in a vast range of species and that in S. cerevisiae NEB comprises a stress response aiding the transport of protein aggregates across the nuclear envelope.

核膜出芽（NEB）是最近发现的一种核质通讯的替代途径，不同于物质通过核孔复合体的运动。通过定量电子显微镜和断层扫描，我们证明了 NEB 从早期原生生物到人类细胞的进化过程中是如何保守的。在酿酒酵母中，在热休克期间、暴露于亚砷酸盐或过氧化氢时以及当蛋白酶体受到抑制时，NEB事件发生的频率更高。用氮杂环丁烷-2-羧酸（一种诱导蛋白质错误折叠的脯氨酸类似物）处理的酵母细胞，NEB 显着增加，表明与蛋白质质量控​​制存在因果关系。泛素和 Hsp104 对蛋白质聚集体的定位和 NEB 事件以及这些结构在热休克过程中的进化进一步支持了这种联系。我们假设 NEB 是许多物种正常细胞生理学的一部分，并且在酿酒酵母中 NEB 包含一种应激反应，有助于蛋白质聚集体跨核膜的运输。