Piezo2 integrates mechanical and thermal cues in vertebrate mechanoreceptors

Abstract

Tactile information is detected by thermoreceptors and mechanoreceptors in the skin and integrated by the central nervous system to produce the perception of somatosensation. Here we investigate the mechanism by which thermal and mechanical stimuli begin to interact and report that it is achieved by the mechanotransduction apparatus in cutaneous mechanoreceptors. We show that moderate cold potentiates the conversion of mechanical force into excitatory current in all types of mechanoreceptors from mice and tactile-specialist birds. This effect is observed at the level of mechanosensitive Piezo2 channels and can be replicated in heterologous systems using Piezo2 orthologs from different species. The cold sensitivity of Piezo2 is dependent on its blade domains, which render the channel resistant to cold-induced perturbations of the physical properties of the plasma membrane and give rise to a different mechanism of mechanical activation than that of Piezo1. Our data reveal that Piezo2 is an evolutionarily conserved mediator of thermal–tactile integration in cutaneous mechanoreceptors.

A dietary fatty acid counteracts neuronal mechanical sensitization

“…Previously, we showed that MA could be efficiently enriched in various cell types and, as a consequence, alter the activation profile of PIEZO1 channels by increasing the plasma membrane structural order and rigidity 25 . Interestingly, previous works suggests that PIEZO1 and PIEZO2 have distinct gating mechanisms 30,51 . For instance, Cox et al 28 demonstrated that PIEZO1 is solely gated by bilayer tension in the absence of the cytoskeleton, whereas current evidence suggests that PIEZO2 gating might depend on the cytoskeleton 8 .…”

Lamellar cells in Pacinian and Meissner corpuscles are touch sensors

“…2G ). In contrast, Meissner lamellar MA currents decayed significantly faster (τ decay = 11.8 ± 2.3 ms, P < 0.0001 versus Pacinian lamellar MA current), similar to mechanoreceptors with fast and intermediate inactivation kinetics ( 27 – 31 ), and lacked a persistent, noninactivating component ( Fig. 2, D and G ).…”

Structure, kinetic properties and biological function of mechanosensitive Piezo channels

“…Recently, sphingomyelinase activity has been revealed to be a crucial determinant of Piezo1 inactivation [ 71 ]. Various modulators, such as pH, temperature, divalent ion concentrations, alternative splicing, osmotic swelling, membrane lipid composition, co-expression of other membrane proteins, and G-protein-coupled pathways have also been reported to regulate the Piezo channel kinetics [ 55 , 72 – 79 ]; however, we still know very little about the relationships among these factors and pivotal structural domains.…”