The molecular basis of force selectivity by PIEZO2 - PubMed
12 hours ago
- #mechanosensation
- #PIEZO2
- #ion channels
- PIEZOs are mechanically gated ion channels that convert force into electrochemical signals.
- PIEZO1 responds to diverse stimuli like membrane stretch and shear stress, while PIEZO2 is specialized for detecting cellular indentation.
- PIEZO2's functional specialization underlies its role in mediating the sense of touch.
- Single-molecule MINFLUX fluorescence nanoscopy and electrophysiology link PIEZO2's conformational states to channel gating in intact cells.
- PIEZO2 is intrinsically more rigid than PIEZO1, and different mechanical stimuli evoke opposite conformational and gating responses in each channel.
- PIEZO2's unique gating properties arise partly from its connection to the actin cytoskeleton, with filamin-B (FLNB) acting as a molecular tether.
- FLNB alters force transmission to PIEZO2, enhancing sensitivity and selectivity for cellular indentation.
- PIEZO2 and FLNB are co-expressed in somatosensory neurons and colocalize at the end organs of cutaneous mechanosensory afferents.
- These findings explain PIEZO2's specialization as a mechanosensor and provide insights into how cells decode diverse mechanical stimuli.