Pushing peristalsis with PIEZO pressure sensor

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Back in 2021, I reported on the Nobel Prize winning discoveries of heat and touch ion channels.

The mechanotransducer ion channel class plays critical roles in addition to the skin’s sense of touch; these include proprioception, skeletal remodeling, maintaining blood pressure, respiration, and bladder control.

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments. The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells. The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far. The regulation of two family members, Piezo1 and Piezo2, has been reported to have essential functions in mechanosensation and transduction in different organs and tissues. Recently, the predominant contributions of the Piezo family were reported to occur in the skeletal system, especially in bone development and mechano-stimulated bone homeostasis. Here we review current studies focused on the tissue-specific functions of Piezo1 and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction. -L Qin, et al.

Mouse Piezo1 protein has a three-bladed, propeller-shaped homotrimeric architecture. a Side view of mouse Piezo1 channel. Piezo1 consists of a central ion-conducting pore modulus (yellow components) and the peripheral mechanotransduction modulus (blue component). The pore module contains the extracellular Cap structure, the transmembrane pore formed from three pairs of TMs, and the intracellular C-terminal domain (CTD). The peripheral mechanotransduction modulus includes a long beam-like structure, a peripheral blade, and a unique anchor domain. The anchor domain formed from a hairpin structure is connected to the CTD plane by the inner helix (IH) and outer helix (OH) pair, which maintains the integrity of the channel. The long beam structure supports and bridges the blade into the central pore module. b Top view of mouse Piezo1 channel. The large extracellular blade domains can curve the plasma membrane, and the three blades are assembled into functional trimers. c Mammalian Piezo1 proteins can be directly gated by membrane stretching, which is conserved throughout evolution. Yoda1 and Jedi1/2 are chemical activators of Piezo channels, and GsMTx4 is an antagonist of the Piezo1 channel. Piezo channels are nonselective cationic mechanosensitive channels that are permeable to alkali ions (K⁺, Na⁺, and Cs⁺), divalent cations (Ba²⁺, Ca²⁺, Mg²⁺, and Mn²⁺), and several organic cations (tetramethyl ammonium (TMA), tetraethyl ammonium (TEA)). Illustrations were modified from Wang et al. and Jiang et al.

Research in mice now implicates these Piezo ion channels in the regulation of gut motility.