PIEZO1 Membrane Protein Introduction

Introduction of PIEZO1

Piezo-type mechanosensitive ion channel component 1 (PIEZO1) is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. PIEZO1 is a large protein containing more than 2,500 amino acids with predicted 24-36 transmembrane domains, depending on the prediction algorithm. PIEZO1 trimeric channels form a three-bladed propeller shape with a central pore formed at the interface of its subunits, determining the ion-conducting properties of PIEZO1. This protein can form non-selective calcium (Ca²⁺)-permeable cation channel. PIEZO1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles.

Function of PIEZO1 Membrane Protein

PIEZO1 is a cation-selective ion channel that is activated in response to mechanical stimuli, which is important for cellular function and PIEZO1 mutations may lead to severe human disorders. The mechanically activated ion channel PIEZO1 is required for lymphatic system function, and homozygous or heterozygous mutations in PIEZO1 have been identified among patients suffering from persistent lymphedema, pleural effusions, and ascites associated with congenital lymphatic dysplasia. In addition, PIEZO1 expressed in endothelial cells plays essential roles in developing blood vessels in mouse embryos and in flow-mediated vasoconstriction in adult mice. Besides, PIEZO1 in red blood cells (RBCs) is shown to regulate cell volume and gain-of-function mutations in PIEZO1 cause dehydrated RBCs and some protection from malaria infection in mice and human. In the central nervous system, PIEZO1 has been demonstrated to be involved in axon guidance of optic tract retinal ganglion cells (RGCs) in the developing Xenopus laevis brain. Taken together, PIEZO1 shows more and more physiological importance in the lymphatic system, CNS, etc.

Fig.1 Structure of the ion channel Piezo1. (Zhao, 2018)

Application of PIEZO1 Membrane Protein in Literature

1. John L.K., et al. The Piezo1 Cation Channel Mediates Uterine Artery Shear Stress Mechanotransduction and Vasodilation During Rat Pregnancy. Am J Physiol Heart Circ Physiol. 2018, 315(4): H1019-H1026. PubMed ID: 30004235
   
   

   The authors in this article firstly implicate a functional role for Piezo1 in the uterine circulation as a mechanosensor of endothelial shear stress. Moreover, the data demonstrate that Piezo1 is upregulated during pregnancy and its activation leads to vasodilation via NO.

2. Tsuchiya M., et al. Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. Nat Commun. 2018, 9(1): 2049. PubMed ID: 29799007
   
   

   This article demonstrates that cell surface flip-flop of phosphatidylserine acts as a molecular switch for PIEZO1 activation that governs proper morphogenesis during myotube formation.

3. Lacroix J.J., et al. Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1. Nat Commun. 2018, 9(1): 2029. PubMed ID: 29795280
   
   

   This article shows that the Piezo1 pore remains fully open if only one subunit remains activated. This study sheds light on the gating and pharmacological mechanisms of a member of the Piezo channel family.

4. Suzuki T., et al. PIEZO1 Channel Is a Potential Regulator of Synovial Sarcoma Cell-Viability. Int J Mol Sci. 2018, 19(5). PubMed ID: 29757938
   
   

   This article suggests that PIEZO1 is highly expressed in SW982 cells and its knockdown affects cell-viability, indicating PIEZO1 as a potential target against synovial sarcoma.

5. Liu Q., et al. Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis. Exp Mol Med. 2018, 50(5): 60. PubMed ID: 29735991
   
   

   This report suggests that the functional role of the Piezo1 channel in CYP-induced chronic cystitis is based on its synergistic effects with NCX1, which can significantly enhance [Ca²⁺] and result in Ca²⁺ overload in bladder ICC-LCs, indicating that the Piezo1 channel and NCX1 are potential novel therapeutic targets for chronic cystitis-associated bladder hyperactivity.

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Reference

1. Zhao Q., et al. (2018). Structure and mechanogating mechanism of the Piezo1 channel. Nature. 554: 487-492.

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