The emerging roles of the endoplasmic reticulum in mechanosensing and mechanotransduction

Cells are continuously subjected to physical and chemical cues from the extracellular environment, and sense and respond to mechanical cues via mechanosensation and mechanotransduction. Although the role of the cytoskeleton in these processes is well known, the contribution of intracellular membranes has been long neglected. Recently, it has become evident that various organelles play active roles in both mechanosensing and mechanotransduction. In this Review, we focus on mechanosensitive roles of the endoplasmic reticulum (ER), the functions of which are crucial for maintaining cell homeostasis. We discuss the effects of mechanical stimuli on interactions between the ER, the cytoskeleton and other organelles; the role of the ER in intracellular Ca²⁺ signalling via mechanosensitive channels; and how the unfolded protein response and lipid homeostasis contribute to mechanosensing. The expansive structure of the ER positions it as a key intracellular communication hub, and we additionally explore how this may be leveraged to transduce mechanical signals around the cell. By synthesising current knowledge, we aim to shed light on the emerging roles of the ER in cellular mechanosensing and mechanotransduction.