Noncanonical role of IRE1 as a mechanotransducer

The endoplasmic reticulum (ER) is the largest organelle in human cells, best known for its role in protein production, quality control, and transport. However, new research is revealing that the ER may also play a critical role in how cells sense and respond to mechanical forces. Since the ER extends throughout the cell, it is exposed to various physical stressesbut its role in mechanobiology remains largely unexplored. Our research focuses on a protein called IRE1, which is well-known for its role in detecting misfolded proteins. We propose a completely new role for IRE1, namely as a mechanosensor, whereby it helps cells detect and respond to mechanical stress. Specifically, we aim to understand how IRE1 is activated by physical stress, how ER structure changes under these conditions, and how this influences protein production. By using cutting-edge techniques in cell biology and microscopy, we will explore this novel function of the ER, challenging the current understanding of cellular mechanotransduction. This study has the potential to redefine the role of the ER in cell biology and could open up new avenues for research in cell mechanics, protein synthesis, and disease mechanisms.