To maintain viability, cells must be able to sense and respond to mechanical stimuli. Despite its fundamental importance, how force is sensed at the molecular level remains largely unknown.
Scientists in the journal Nature Communications show that stomatin-like protein-3 (STOML3) protein acts in mechanosensation by binding cholesterol and regulating membrane stiffness which can in turn regulate ion flux through mechanosensitive channels including Piezo channels.
STOML3 is detected in cholesterol-rich lipid rafts. In mouse sensory neurons, depletion of cholesterol and deficiency of STOML3 similarly and interdependently attenuate mechanosensitivity while modulating membrane mechanics.
In heterologous systems, intact STOML3 is required to maintain membrane mechanics to sensitize Piezo1 and Piezo2 channels.
In C57BL/6N, but not STOML3−/− mice, tactile allodynia is attenuated by cholesterol depletion, suggesting that membrane stiffening by STOML3 is essential for mechanical sensitivity.
Targeting the STOML3–cholesterol association might offer an alternative strategy for control of chronic pain.