Piezo proteins are the pore-forming subunits of trimeric mechanosensitive ion channels that open in response to mechanical stimuli such as shear stress and membrane stretch, allowing positively charged ions, including calcium, to flow into the cell. Piezo orthologs have thus far been identified in numerous eukaryotes. Most vertebrates have two channel isoforms, Piezo1 and Piezo2. Across species, Piezos are very large proteins (2521 and 2752 amino acids for human Piezo1 and human Piezo2, respectively) with numerous (>14) predicted TM domains per subunit and, strikingly, no homology to other known proteins [6]. Piezo channels play a critical role in sensory neuron transduction [2,7]

Yoda1 is a Piezo1 channel activator [1,4].

* Key recommended reading is highlighted with an asterisk

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* Douguet D, Patel A, Xu A, Vanhoutte PM, Honoré E. (2019) Piezo Ion Channels in Cardiovascular Mechanobiology. Trends Pharmacol Sci, 40 (12): 956-970. [PMID:31704174]

* Ehmke H. (2018) The mechanotransduction of blood pressure. Science, 362 (6413): 398-399. [PMID:30361358]

* Gottlieb PA, Sachs F. (2012) Piezo1: properties of a cation selective mechanical channel. Channels (Austin), 6 (4): 214-9. [PMID:22790400]

* Kefauver JM, Ward AB, Patapoutian A. (2020) Discoveries in structure and physiology of mechanically activated ion channels. Nature, 587 (7835): 567-576. [PMID:33239794]

* Murthy SE, Dubin AE, Patapoutian A. (2017) Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol, 18 (12): 771-783. [PMID:28974772]

* Parpaite T, Coste B. (2017) Piezo channels. Curr Biol, 27 (7): R250-R252. [PMID:28376327]

* Tang H, Zeng R, He E, Zhang I, Ding C, Zhang A. (2022) Piezo-Type Mechanosensitive Ion Channel Component 1 (Piezo1): A Promising Therapeutic Target and Its Modulators. J Med Chem, 65 (9): 6441-6453. [PMID:35466678]

* Volkers L, Mechioukhi Y, Coste B. (2015) Piezo channels: from structure to function. Pflugers Arch, 467 (1): 95-9. [PMID:25037583]

* Wu J, Lewis AH, Grandl J. (2017) Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels. Trends Biochem Sci, 42 (1): 57-71. [PMID:27743844]

* Xiao B. (2020) Levering Mechanically Activated Piezo Channels for Potential Pharmacological Intervention. Annu Rev Pharmacol Toxicol, 60: 195-218. [PMID:31454291]

Yang X, Lin C, Chen X, Li S, Li X, Xiao B. (2022) Structure deformation and curvature sensing of PIEZO1 in lipid membranes. Nature, 604 (7905): 377-383. [PMID:35388220]

* Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Patapoutian A. (2018) PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science, 362 (6413): 464-467. [PMID:30361375]

1. Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM, Hyman AJ, Hall SJ, Gaunt HJ, Ludlow MJ, Foster R et al.. (2018) Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br J Pharmacol, 175 (10): 1744-1759. [PMID:29498036]

2. Murthy SE, Loud MC, Daou I, Marshall KL, Schwaller F, Kühnemund J, Francisco AG, Keenan WT, Dubin AE, Lewin GR et al.. (2018) The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci Transl Med, 10 (462). [PMID:30305457]

3. Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, Lao J, Tully DC, Engels IH et al.. (2015) Chemical activation of the mechanotransduction channel Piezo1. Elife, 4. [PMID:26001275]

4. Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S. (2016) Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J Clin Invest, 126 (12): 4527-4536. [PMID:27797339]

5. Wang Y, Chi S, Guo H, Li G, Wang L, Zhao Q, Rao Y, Zu L, He W, Xiao B. (2018) A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun, 9 (1): 1300. [PMID:29610524]

6. Wu J, Lewis AH, Grandl J. (2017) Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels. Trends Biochem Sci, 42 (1): 57-71. [PMID:27743844]

7. Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Patapoutian A. (2018) PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science, 362 (6413): 464-467. [PMID:30361375]