Piezo2 is a non-selective mechanically-activated cation channel (Coste, 2010). It has a pivotal role in light-touch sensation and proprioception (Woo SH, 2014, Ranade S, 2014, Woo SH, 2015) and is highly expressed in the dorsal root ganglia, lungs and bladder (Coste, 2010). Piezo2 ubiquitous KO mice die perinatally for respiratory distress.
Piezo2 is responsible of Merkel cell sustained depolarization and slowly adapting Aβ fibres firing rate (Maksimovic, 2014). Skin-specific Piezo2-KO mice show reduced slowly adapting responses (Woo SH, 2014). Mice lacking Piezo2 in both Merkel cells and sensory neurons exhibit a profound loss of touch sensation, while thermal stimuli and noxious mechanical forces showed similar responses (Ranade SS, 2014).
Piezo2 is also expressed in muscle spindles and Golgi-tendon organs. Mice lacking its expression in proprioceptors show decreased stretch-induced firing in muscle-nerve recordings (Woo SH, 2015).
Its expression is also present in vagal and spinal sensory neurons innervating the lungs, where it functions as a stretch sensor upon lung inflation. Mice lacking Piezo2 in these neurons show reduced vagal nerve firing in response to lung inflation (Nonomura K, 2016).
Arthrogryposis, distal, with impaired proprioception and touch (DAIPT)
DAIPT is caused by biallelic variants of PIEZO2. The following are the reported variants:
- Pakistani (homozygous, c.493-?_917+?del, p.fs*);
- Turkish (homozygous, c.1384C>T, p.R462*);
- Lybian (homozygous, c.1550_1552delGCTinsCGAA, p.S517fs48*);
- Bangladeshi (homozygous, c.2708C>G, p.S903*);
- Indian (homozygous, c.3019_3029del11, p.P1007Lfs3*);
- Bangladeshi (compound heterozygous, c.4723C>T, p.R1575*; c.5053C>T, p.R1685*);
- European, Japanese (compound heterozygous, c.5053C>T, p.R1685*; c.5054G>C, p.R1685P);
- Turkish (homozygous, c.5621delT, p.L1874Rfs5*).
The main hypothesis is that these variants cause a loss-of-function of the channel, due to reduced levels of PIEZO2 expression and/or expression of a truncated and thus not functional protein (Delle Vedove, 2016; Chesler, 2016).