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.
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 plays a crucial role in maintaining endoplasmic reticulum (ER) 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.’
An essential component of this protein folding factory is PERK. PERK is known to detect protein folding errors in the cell.
Researchers at the Laboratory of Cell Death Research & Therapy at KU
Leuven (University of Leuven, Belgium) have now revealed a hidden perk:
the protein also coordinates the communication between the inside and
the outside of the cell. These findings open up new avenues for further
research into treatments for cancer, Alzheimer's, and diabetes.
"This protein is known to play a crucial role in maintaining ER
functions and restoring them if necessary," explains Patrizia Agostinis,
head of the KU Leuven Laboratory of Cell Death Research & Therapy.
"When PERK detects protein folding errors in the ER it prompts the
nucleus of the cell to take action."
Patrizia Agostinis, Alex van Vliet, and other team members have now
discovered an additional function of PERK. Agostinis: "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. After all, calcium is
crucial for the proper functioning of the protein folding factory - the
ER, where the calcium is stored - and for the overall health of the
cell. And 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."
"This entire process, which is regulated by PERK, takes place in a
matter of minutes or even seconds," Alex van Vliet adds. "That's 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 newly discovered role of PERK opens up promising therapeutic
avenues. "But we must not get ahead of ourselves," Agostinis emphasizes.
"This is fundamental research. Much more work needs to be done before
we can even start thinking of new treatments that target this new
function of PERK."