Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 42; no. 1; pp. 57 - 71
• Main Authors: Wu, Jason, Lewis, Amanda H., Grandl, Jörg
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2017
• Subjects: Humans; Ion Channels - metabolism; Mechanotransduction, Cellular
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2016.09.004

In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. Here, we review these findings and discuss the many aspects of Piezo function that remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function. Piezo proteins were identified in 2010 as the pore-forming subunits of excitatory mechanosensitive ion channels. Piezo ion channels play essential roles in diverse physiological processes ranging from regulation of red blood cell volume to sensation of gentle touch, and are associated with a number of diseases. A recent medium-resolution structure gives insight into the overall architecture of Piezo1, but does not give straight answers as to how the channel transduces mechanical force into pore opening. The function of Piezos, including the inactivation mechanism, can be modulated by many factors both intrinsic and extrinsic to the channel.