Filaments of actin in super resolution. Actin makes up the cell skeleton, which gives structure to the cell and allows for movement. Photo: Alex van Vliet
Feb 27 2017 Posted: 11:45 GMT

Project coordinated by NUI Galway, releases new findings on cell communication leading to further research into treatments for cancer, Alzheimer’s and diabetes

The Horizon 2020 funded project TrainERS coordinated by NUI Galway, has released new findings on how communication is coordinated between the inside and outside of a cell. The discovery is set to open up new avenues for further research into treatments for Alzheimer’s, cancer and diabetes.

The discovery was made by researchers at the Laboratory of Cell Death Research and Therapy at the University of Leuven in Belgium. TrainERS is being coordinated by Professor Afshin Samali, CÚRAM Researcher and Professor of Biochemistry and Director of the Apoptosis Research Centre (ARC) at NUI Galway. The findings were published in the scientific journal Molecular Cell of which Professor Samali and his colleagues in Belgium are co-authors.

Proteins such as insulin are properly formed in the endoplasmic reticulum (ER), one of the biggest membrane structures in the cell. The ER works like an assembly line and folds the proteins into a three-dimensional shape that is essential for them to function. When there is a problem in the ‘protein folding assembly line’, the accumulation of misfolded proteins can lead to diseases such as Alzheimer’s, cancer, and diabetes.

PERK, an enzyme known to detect protein folding errors in the cell has now also been revealed to coordinate the communication between the inside and the outside of the cell, and is an essential component of this protein folding factory.

Commenting on the new findings, Professor Afshin Samali of NUI Galway said: “This is an extremely exciting step forward for any researcher involved in understanding the ER stress response mechanistically and quantitatively. I would like to congratulate the researchers involved and look forward to more exciting developments to come out of the TrainERS programme.”

Patrizia Agostinis, Alex van Vliet, and other team members at the University of Leuven discovered the additional function of PERK. “This protein is known to play a crucial role in maintaining endoplasmic reticulum functions and restoring them if necessary. When PERK detects protein folding errors in the ER it prompts the nucleus of the cell to take action”, explains Patrizia Agostinis, head of the Laboratory of Cell Death Research and Therapy in the University of Leuven. 

“We found that PERK also coordinates the communication between the protein folding factory (the ER) and the skin of the cell (the plasma membrane). When the protein folding factory detects low calcium levels, the plasma membrane needs to let calcium flow back in. Calcium is crucial for the proper functioning of the protein folding factory where the calcium is stored, and for the overall health of the cell. This is where PERK comes in: the protein establishes contact between the two cell components so that they can work together to restore the calcium level”, added Ms Agostinis.

Mr Alex van Vliet from the University of Leuven added, “This entire process, which is regulated by PERK, takes place in a matter of minutes or even seconds. That is one of the reasons why it went unnoticed until now. We used a new method to reveal the underlying mechanism, and were surprised to find that PERK can control the movement of the ER towards the plasma membrane by modifying the skeleton of the cell.”

The project is funded by Research Foundation Flanders (FWO) and by TrainERS, an innovation training network funded by Horizon 2020 and coordinated by CÚRAM at NUI Galway. Alex van Vliet received funding from the Flemish government agency for Innovation by Science and Technology (IWT).

The TrainERS consortium is coordinated by NUI Galway with partners University of Bordeaux, Goethe-University Frankfurt, University of Leuven, Royal College of Surgeons in Ireland, Medical University of Vienna, Imperial College London, Bellvitge Biomedical Research Institute, University of Gothenburg and Randox Teoranta.

To read the full research paper in Molecular Cell visit:  http://www.sciencedirect.com/science/article/pii/S1097276517300461

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