Abstract
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.
Highlights
Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex
We show the presence of nuclear envelope budding (NEB) in five different evolutionarily distant organisms (Homo sapiens, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Trypanosoma brucei) under normal growth conditions, which reveals the evolutionary conservation of the NEB pathway
NEB remains viewed as an irregularity rather than a normal route for transport over the nuclear envelope in healthy mature cells
Summary
Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Herpes simplex virus replicates in the nucleoplasm and is released into the cytosol via an outward budding of the nuclear envelope [10,11,12,13] This demonstrates another pathway for nuclear export, and there have been several observations suggesting that nuclear envelope budding (NEB) occurs in healthy cells, with different interpretations of this mechanism being suggested [14,15,16,17,18,19,20,21,22,23,24,25,26,27]. As well as transporting material from the nucleus to the cytoplasm, NEB can result in the transfer of a portion of the Significance
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