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Piezos thrive under pressure: mechanically activated ion channels in health and disease

Nature Reviews Molecular Cell Biology volume 18, pages 771–783 (2017)Cite this article

Subjects

Key Points

  • Piezos are bona fide mechanically activated ion channels that have a leading role in several cellular mechanotransduction events.

  • Piezo proteins are unique in their size and lack homology to other membrane proteins. However, recent structural and functional studies have started to unravel architectural features of the channel.

  • Piezo ion channels are activated by various physiologically relevant physical forces.

  • The Piezo1 channel is involved in cardiovascular mechanotransduction, red blood cell volume regulation and epithelial homeostasis, and the Piezo2 channel is involved in sensory and respiratory mechanotransduction.

  • Several genetic disorders linked to mutations in PIEZO1 and PIEZO2 have helped to uncover unexpected roles for mechanotransduction in mammalian physiology.

Abstract

Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.

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Figure 1: Topology and structural orientation of Piezo1.
Figure 2: Models of activation for Piezo channels.
Figure 3: Physiological role of Piezo channels.

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Acknowledgements

The authors thank J. Kefauver, K. Marshall and K. Saotome for their helpful comments. A.P. is a Howard Hughes Medical Institute investigator.

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  1. Department of Neuroscience, Howard Hughes Medical Institute, The Scripps Research Institute, La Jolla, 92037, California, USA

    Swetha E. Murthy, Adrienne E. Dubin & Ardem Patapoutian

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A.P., S.E.M. and A.E.D. discussed the content of the article and contributed to the writing and editing of the manuscript. S.E.M. and A.E.D. also contributed by researching data for the article.

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Correspondence to Ardem Patapoutian.

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The authors declare no competing financial interests.

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Glossary

Membrane potential

The voltage across the plasma membrane that is dependent on the charge separated on the outer and inner membrane leaflets; usually, the resting membrane potential is negative (∼−70 to −30 mV depending on the cell type).

Lipid rafts

Membrane subdomains that are ordered assemblies enriched in cholesterol, glycosphingolipids and proteins.

Bradykinin

An inflammatory peptide that activates cognate G protein-coupled receptors.

Dorsal root ganglion (DRG) neurons

Pseudo-unipolar sensory neurons whose cell bodies are located in the dorsal root of the spinal column and extend a single bifurcating axon, one end of which innervates sensory organs and the other which synapses onto neurons in the spinal cord. They are capable of detecting mechanical, chemical and/or thermal stimuli and signal to the central nervous system.

Pericentrin

A multifunctional scaffold for anchoring proteins and protein complexes.

Transient receptor potential cation channel subfamily V member 1

(TRPV1). An ion channel activated by capsaicin and heat that is expressed in a subpopulation of sensory neurons, including nociceptors.

Calpain

A calcium-dependent cytosolic cysteine proteinase with roles in cell migration, differentiation and apoptosis.

Focal adhesions

Contact sites between cells and the extracellular matrix that function as anchor points for the cell and as biochemical signalling centres.

Traction force

A type of force generated within the cell in response to change in its environment. These forces are a result of interactions between actin filaments, adhesion molecules and the extracellular matrix.

Nociceptors

A subpopulation of non-myelinated or lightly myelinated sensory neurons that detect noxious stimuli and are the initial receptors that signal the presence of a stimulus that can cause damage to the organism.

Merkel cells

Specialized epithelial cells present in the skin that are in close contact with the peripheral terminals of low-threshold sensory neurons.

Vagal neurons

Sensory neurons that have their cell bodies within the nodose and jugular ganglia situated in the vagus nerve (tenth cranial nerve) and that innervate internal organs.

Arthrogryposis

A condition characterized by joint contractures causing immobility of the joints, which is generally associated with other disorders.

Enterochromaffin cells

A subset of cells in the epithelium of the lumen of the gastrointestinal tract that regulates secretion of enzymes and bowel movement.

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Murthy, S., Dubin, A. & Patapoutian, A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol 18, 771–783 (2017). https://doi.org/10.1038/nrm.2017.92

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