A new function for the nucleolus

The nucleolus is a structure found in the nucleus of the cell and was described for the first time in the 1830s. It is not separated from the rest of the cell by a membrane as is the case with other organelles and cell structures.

In the 1960s it was discovered that its main function was to be the place where ribosomes are assembled, which in turn are responsible for synthesizing (making) proteins.

For some time, it has been known that proteins called chaperones move within the nucleolus under certain circumstances. It had been suggested that this relocation was related to protein synthesis. However, this new work shows that chaperones that migrate to the nucleus are bound to stress-sensitive proteins.

[box type = »info» align = »» class = »» width = »»] Chaperone proteins are a set of proteins present in all cells, many of which are heat shock proteins, whose function is to help to the folding of other newly formed proteins in protein synthesis.

These chaperones are not part of the primary structure of the functional protein, but only bind to it to help in its folding, assembly and cellular transport to another part of the cell where the protein performs its function.

The nucleolus as a place of protection and quality control of proteins

When cells are under stress, proteins tend to fold and aggregate. To prevent agglomeration, some of them are temporarily stored in the nucleolus. This organelle has special biophysical conditions that prevent the harmful aggregation of proteins.

This is the fruit of research carried out by Ralf Jungmann, Professor of Experimental Physics at LMU and Leader of the Molecular Imaging and Bionanotechnology Group at the Max Planck Institute (MPI) for Biochemistry, in cooperation with F.-Ulrich Hartl and Mark Hipp (both based on the MPI for Biochemistry) which has been published in Science .

F.-Urich Hartl’s team is a pioneer in chaperone research and had already discovered that in addition to what was explained above, chaperones are crucial for the correct folding of proteins and play a central role in protein quality control .

If the proteins are not folded correctly, the misfolded forms of the proteins can accumulate and clump together. This aggregate resulting from protein misfolding can be seen very often in neurodegenerative diseases such as Alzheimer’s , Parkinson’s or Huntington’s.

How the discovery came about

Mark Hipp, a member of the F. -Ulrich Harlts team explains that: “We have been using the enzyme luciferase as a protein model for many years to investigate the mechanisms of protein folding.”

By fusing the enzyme with a fluorescent protein, scientists can trace it under the microscope and see if the protein is correctly folded or misfolded and if it forms clumps.

“We were able to show that stress on cells by heating them to 43 ° C results in the transport of misfolded luciferase protein, along with chaperones, to the nucleolus.”


To elucidate the mechanical details of this process, the researchers cooperated with groups led by Ralf Jungmann, who developed a series of high-resolution fluorescence techniques, and Jürgen Cox (also at the MPI for Biochemistry), who contributed new methods of bioinformatic analysis.

Together they were able to show that the misfolded luciferase protein behaved differently within the nucleolus than in the rest of the cell. “In the nucleolus, the misfolded proteins remained in a liquid-like state rather than aggregated,” explains Frédéric Frottin, first author of the study. This is possible due to the specific biophysical conditions that prevail within the organelle.

‘Proteins that generally tend to aggregate are stored in a less dangerous way during stress, which protects cells from damage. Once the cell has had time to recover, the proteins can fold back and be released from the nucleolus, ”continues Frottin. At this point, cells have the ability to activate other mechanisms that allow the protein to be repaired or degraded.

The researchers also showed that this protective mechanism fails if cellular stress lasts too long. “This is a new mechanism that maintains the integrity of the cell,” says Mark Hipp. The maintenance of this integrity is essential to inhibit the development of the disease and delay the aging process.

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