Piezo1, a non-selective cation channel directly activated by mechanical forces, is widely expressed in the digestive system and participates in biological functions physiologically and pathologically.
1. Mechanosensitive Ion Channels in the Digestive System
Mechanotransduction refers to the process of living mechanosensitive tissues or cells to detect and respond to changes in membrane tension and cytoskeleton induced by mechanical stimuli, initiating intracellular signal transduction and generating electrochemical signals
[1,2][1][2]. The digestive system experiences various mechanical stimuli, including gastrointestinal peristalsis, villus movement, conduit osmotic pressure, etc, which are fundamental for initiating mechanotransduction. Mechanotransduction relies on ion channels sensitive to mechanical stimuli, which are known as mechanosensitive ion channels. The mechanosensitive ion channels in digestive system include transient receptor potential vanilloid family (TRPV)
[3], Piezo1/2
[4], two pore-domain potassium channels (K2p)
[5], large-conductance Ca
2+-activated potassium channel (BKCa)
[6] and others.
The Piezo protein, characterized as the largest plasma membrane ion channel complex with over 30 putative transmembrane domains, is a unique entity capable of inducing large mechanically-activated cationic currents unlike other known ion channels or proteins
[7]. At present, Piezo channel has drawn considerable research interest
[8]. Piezo protein contains two homologues in
Homo sapiens, Piezo1 and Piezo2 (
Table 1). Compared with Piezo1, Piezo2 has additional charged residues at the beam-carboxy-terminal domain interface and additional constriction sites at L2743, F2754 and E2757 in the central pore
[9,10][9][10]. Piezo1 is widely expressed in multiple cell types, whereas Piezo2 is believed to be predominantly expressed in neurons and intestinal enterochromaffin cells.
First identified in 2010 by Coste B
[11], Piezo1 (Fam38a) plays important roles in maintaining various cellular effects such as bone and epithelial homeostasis, neural stem cell differentiation, macrophage polarization, and regulating biological functions including vascular development, red blood cell volume homeostasis, inflammation response generation and etc.
[12,13,14,15][12][13][14][15]. More recently, Piezo1 channel has also been identified to transduce itch in sensory neuron which is associated with Piezo2 channel as generally believed
[16]. Therefore, Piezo1 participates in life activity widely and deeply. And more and more evidences have demonstrated the predominant and special contributions of the Piezo1 channel in the digestive system at present
[4].
hRe
re we review current studiessearchers focused on the cellular effects of Piezo1 in digestive system, with special highlights on its importance in regulating biological function.
Table 1.
Differences between Piezo1 and Piezo2.
|
Piezo1 |
Study |
Piezo2 |
Study |
Gene region |
16q24.3 |
[12] |
18p11.22-p11.21 |
[17] |
* detected in HEK293T cell line.