Adenosine Triphosphate Release and P2 Receptor Signaling in Piezo1 Channel-Dependent Mechanoregulation.

Linyu Wei,Sébastien Roger,Dongliang Li,Xuebin Yang,Fatema Mousawi,Lin-Hua Jiang,Jing Li

doi:10.3389/fphar.2019.01304

Abstract

Organs and tissues and their constituent cells are physiologically submitted to diverse types of mechanical forces or stress, one common sequence of which is release of intracellular ATP into extracellular space. Extracellular ATP is a well-established autocrine or paracrine signaling molecule that regulates multiple cell functions and mediates cell-to-cell communications via activating the purinergic P2 receptors, more specifically, ligand-gated ion channel P2X receptors and some of the G-protein-coupled P2Y receptors. The molecular mechanisms that sense mechanical and transduce forces to trigger ATP release are poorly understood. The Piezo1, a newly identified mechanosensing ion channel, shows widespread expression and confers mechanosensitivity in many different types of cells. In this mini-review, we briefly introduce the Piezo1 channel and discuss the evidence that supports its important role in the mechanoregulation of diverse cell functions and, more specifically, critical engagement of ATP release and subsequent P2 receptor activation in Piezo1 channel-dependent mechanoregulation. Such ATP release-mediated coupling of the Piezo1 channel and P2 receptors may serve a signaling mechanism that is more common than we currently understand in transducing mechanical information to regulation of the attendant cell functions in various organs and tissues.

Highlights

Adenosine triphosphate (ATP), while it is best known for its intracellular role as the cellular energy source, gains increasing recognition as an extracellular signaling molecule when it is released into extracellular spaces
It is worth mentioning that the vesicular nucleotide transporter (VNUT) plays a critical role in mediating vesicular storage and thereby subsequent release of ATP (Sawada et al, 2008)
With increasing evidence to show their overlapping expression in many different types of mechanosensitive cells, the Piezo1 channel and P2 receptors, via coupling by ATP, may serve as a signaling mechanism that is more common than we currently understand in transducing the mechanical information to functional regulation

Summary

INTRODUCTION

Adenosine triphosphate (ATP), while it is best known for its intracellular role as the cellular energy source, gains increasing recognition as an extracellular signaling molecule when it is released into extracellular spaces. Piezo1-Dependent ATP Release in Mechanoregulation ecto-nucleotidases that convert ATP to ADP, adenosine monophosphate, or adenosine (Figure 1) (Verkhratsky and Burnstock, 2014; Jiang et al, 2017a) This system represents one of the most common signaling mechanisms regulating cell functions and mediating cell-to-cell communications and plays a critical role in a wide range of physiological processes, such as hearing, tasting, nociception, immune responses, muscle contraction, learning, and memory. The two separate domains of investigation need to join forces in order to develop a full and mechanistic understanding of mechanoregulation The aim of this minireview is to introduce the Piezo channel and discuss the recent studies that provide evidence to support its crucial role in several types of mechanosensitive cells in the induction of ATP release and subsequent activation of the P2X or P2Y receptors and the mechanoregulation of the attendant cell functions. With increasing evidence to show their overlapping expression in many different types of mechanosensitive cells, the Piezo channel and P2 receptors, via coupling by ATP, may serve as a signaling mechanism that is more common than we currently understand in transducing the mechanical information to functional regulation

A Brief Introduction to the Piezo1 Channel

Findings

CONCLUDING REMARKS