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Piezo1

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Target id: 2945

Nomenclature: Piezo1

Family: Piezo channels

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 36 2521 16q24.3 PIEZO1 piezo type mechanosensitive ion channel component 1
Mouse 35 2547 8 E1 Piezo1 piezo-type mechanosensitive ion channel component 1
Rat 35 2535 19q12 Piezo1 piezo-type mechanosensitive ion channel component 1
Gene and Protein Information Comments
Piezo proteins have between 24 and 36 predicted transmembrane (TM) domains, although a much lower number (14) of TM domains are resolved in the Piezo1 structure than initially predicted through topology software [1].
Previous and Unofficial Names Click here for help
FAM38A | family with sequence similarity 38, member A | DHS | Mib | LMPH3
Database Links Click here for help
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM study of the mammalian mechanosensitive Piezo1 channel
PDB Id:  3JAC
Resolution:  4.8Å
Species:  Mouse
References:  3
Functional Characteristics Click here for help
Mechano-activated

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Yoda1 Small molecule or natural product Mm Activation 4.8 pEC50 - no 6
pEC50 4.8 (EC50 1.71x10-5 M) [6]
Not voltage dependent
Yoda1 Small molecule or natural product Primary target of this compound Hs Activation 4.6 pEC50 - no 6
pEC50 4.6 (EC50 2.66x10-5 M) [6]
Not voltage dependent
Jedi2 Small molecule or natural product Primary target of this compound Mm Activation 3.8 pEC50 - no 7
pEC50 3.8 (EC50 1.58x10-4 M) [7]
Not voltage dependent
Description: Measuring calcium flux (GCAMP6s fluorescence) in mPiezo1-transfected HEK293T cells.
Jedi1 Small molecule or natural product Ligand has a PDB structure Mm Activation - - - no 7
[7]
Not voltage dependent
View species-specific activator tables
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
Dooku1 Small molecule or natural product Hs Inhibition 5.8 – 5.9 pIC50 - no 2
pIC50 5.9 (IC50 1.3x10-6 M) [2]
Not voltage dependent
Description: Measuring antagonism of Yoda1-mediated calcium entry in HEK293 cells exogenously expressing human Piezo1 channels.
pIC50 5.8 (IC50 1.5x10-6 M) [2]
Not voltage dependent
Description: Measuring antagonism of Yoda1-mediated calcium entry in HUVEC cells which endogenously express Piezo1 channels.
Immunopharmacology Comments
Work by Liu et al. (2018) shows that Piezo1 is involved in immune regulation [4]. Piezo1 signalling appears to cause a rearrangement of the actin scaffold, that connects this mechanosensor's function to optimal T cell receptor signalling and T cell activation. Knock out of Piezo1 channels in the innate immune cells of mice has shown that mechanosensation of force by Piezo1 in the lung is an essential component of innate immune system-mediated inflammatory reponses [5].
Cell Type Associations
Immuno Cell Type:  T cells
Comment:  Piezo1 mechanosensors are involved in the optimisation of human T cell activation and in T cell proliferation.
References:  4

References

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1. Coste B, Murthy SE, Mathur J, Schmidt M, Mechioukhi Y, Delmas P, Patapoutian A. (2015) Piezo1 ion channel pore properties are dictated by C-terminal region. Nat Commun, 6: 7223. [PMID:26008989]

2. 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]

3. Ge J, Li W, Zhao Q, Li N, Chen M, Zhi P, Li R, Gao N, Xiao B, Yang M. (2015) Architecture of the mammalian mechanosensitive Piezo1 channel. Nature, 527 (7576): 64-9. [PMID:26390154]

4. Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR, Rahaman O, Talukdar A, Ganguly D. (2018) Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation. J. Immunol., 200 (4): 1255-1260. [PMID:29330322]

5. Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG et al.. (2019) Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature, 573 (7772): 69-74. [PMID:31435009]

6. 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]

7. 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]

How to cite this page

Piezo channels: Piezo1. Last modified on 26/08/2019. Accessed on 24/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2945.