What is it about?
We describe a route of transport over the nuclear membrane using budding. This route of transport was used in all different cell types we looked at, and it increased when the cells were stressed with heat, arsenic, H2O2 and age. We can detect proteins usually associated with misfolded proteins in the budding events and when we exposed cells the a drug that induces protein misfolding we saw the highest amount of nuclear budding events, showing that this transport is important for protein quality control.
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Why is it important?
A defining feature of eukaryotes is the nuclear envelope, a double lipid bilayer that serves to isolate and protect the cell’s genetic material. Transport of large molecules over this barrier is believed to occur almost exclusively via the nuclear pores. However, herpes virions and mega-ribonucleoproteins (megaRNPs) use an alternative means of transport—via nuclear envelope budding (NEB). Here, we show NEB is a ubiquitous eukaryotic phenomenon and increases when exposed to various forms of cellular stress. NEB frequency was maximal when the cell was challenged with a drug that induces protein misfolding, indicating this transport pathway plays a role in protein quality control. These results imply that NEB is an under-appreciated yet potentially fundamental means of nuclear transport.
Perspectives
This project arouse from an observation I saw 20 years ago as a PhD student. Over the years working with electron microscopy I had seen these events in many different cell types, and this project started with a quantification to see if this really was a "thing". The project then ran took its own life and somehow snowballed into this publication. It is the first time in my career this happens and it was very exciting to follow this science unfold.
Johanna Hoog
Read the Original
This page is a summary of: Nuclear envelope budding is a response to cellular stress, Proceedings of the National Academy of Sciences, July 2021, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2020997118.
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