PIEZO1

Last updated
PIEZO1
Identifiers
Aliases PIEZO1 , DHS, FAM38A, Mib, LMPH3, piezo type mechanosensitive ion channel component 1, LMPHM6
External IDs OMIM: 611184; MGI: 3603204; HomoloGene: 124356; GeneCards: PIEZO1; OMA:PIEZO1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001142864

NM_001037298
NM_001357349

RefSeq (protein)

NP_001136336

n/a

Location (UCSC) Chr 16: 88.72 – 88.79 Mb Chr 8: 123.21 – 123.28 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

PIEZO1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. PIEZO1 and its close homolog PIEZO2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels. [5]

Contents

Structure and function

PIEZO1 (this gene) and PIEZO2 share 47% identity with each other and they have no similarity to any other protein and contain no known protein domains. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed PIEZO1 is the pore-forming subunit of a mechanosensitive channel. [6] This new " PIEZO" family is catalogued as InterPro :  IPR027272 and TCDB 1.A.75 . PIEZO1 homologues are found in C. elegans and Drosophila , which, like other invertebrates, have a single PIEZO protein.

It is known ( PDB: 6B3R ) that PIEZO1 channel is a three-bladed propeller-like structure. A lever-like mechanogating mechanism is assumed. [7] [8]

Image of PIEZO1 homotrimer (left: from the side, right: from the top) created with PyMOL from PDB: 5Z10 . Piezo1 homotrimer.png
Image of PIEZO1 homotrimer (left: from the side, right: from the top) created with PyMOL from PDB: 5Z10 .

Tissue distribution

PIEZO1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles. Unlike PIEZO2 which is highly expressed in sensory dorsal root ganglia, PIEZO1 is not expressed in sensory neurons. [5] Consequently PIEZO1 plays a significant role in multiple neurobiological processes including axon regeneration, neural stem cells differentiation and neurological diseases progression. [9]

PIEZO1 is also expressed in immune cells, including lymphocytes and myeloid cells, and has been shown to have a role in the function of fundamental immune processes, like antigen presentation and phagocytosis. [10] [11] [12]

Levels of PIEZO1 mRNA have been shown to be increased by mechanical stimulation, such as vibration at 1,000 Hz in monocytes. [13]

Clinical significance

PIEZO1 is also found in red blood cells, and gain of function mutations in the channels are associated with hereditary xerocytosis or stomatocytosis. [14] [15] [16] PIEZO1 channels are pivotal integrators in vascular biology. [17]

An allele of PIEZO1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to Plasmodium . This allele has been demonstrated in vitro to prevent cerebral malaria infection. [18]

PIEZO1 has been implicated in extrusion of epidermal cells when a layer becomes too confluent to preserve normal skin homeostasis. This acts to prevent excess proliferation of skin tissue, and has been implicated in cancer biology as a contributing factor to metastases by assisting living cells in escaping from a monolayer. [19]

Expression of murine PIEZO1 in mouse innate immune cells is essential for their function, a role mediated by sensing mechanical cues. Deficiency in PIEZO1 in mice lead to increased susceptibility of myeloid cells to infection by Pseudomonas aeruginosa . [20]

Lymphatic malformation 6 syndrome is caused by mutations in PIEZO1 and was characterized in 2015. [21]

PIEZO1 has been proposed as a therapeutic target for Alzheimer's disease. The build-up of amyloid-β plaques stiffen the brain's structure. Microglial maintenance cells, which express PIEZO1, detect this stiffness via PIEZO1-enabled mechanosensation and in response surround, compact, and phagocytosize the plaques. Removal of the gene which codes for PIEZO1 in microglia decreases plaque clearance and hastens cognitive decline in rats. [22]

Ligands

Agonists

Antagonists

Related Research Articles

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<span class="mw-page-title-main">Hereditary stomatocytosis</span> Medical condition

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Mechanosensation is the transduction of mechanical stimuli into neural signals. Mechanosensation provides the basis for the senses of light touch, hearing, proprioception, and pain. Mechanoreceptors found in the skin, called cutaneous mechanoreceptors, are responsible for the sense of touch. Tiny cells in the inner ear, called hair cells, are responsible for hearing and balance. States of neuropathic pain, such as hyperalgesia and allodynia, are also directly related to mechanosensation. A wide array of elements are involved in the process of mechanosensation, many of which are still not fully understood.

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<span class="mw-page-title-main">PIEZO2</span>

Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene. It has a homotrimeric structure, with three blades curving into a nano-dome, with a diameter of 28 nanometers.

<span class="mw-page-title-main">Yoda1</span> Chemical compound

Yoda1 is a chemical compound which is the first agonist developed for the mechanosensitive ion channel PIEZO1. This protein is involved in regulation of blood pressure and red blood cell volume, and Yoda1 is used in scientific research in these areas.

<span class="mw-page-title-main">Ardem Patapoutian</span> Molecular biologist, neuroscientist, and Nobel laureate 2021

Ardem Patapoutian is a Lebanese-American molecular biologist, neuroscientist, and Nobel Prize laureate of Armenian descent. He is known for his work in characterizing the PIEZO1, PIEZO2, and TRPM8 receptors that detect pressure, menthol, and temperature. Patapoutian is a neuroscience professor and Howard Hughes Medical Institute investigator at Scripps Research in La Jolla, California. In 2021, he won the Nobel Prize in Physiology or Medicine jointly with David Julius.

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<span class="mw-page-title-main">Jedi1</span> Chemical compound

Jedi1 is a chemical compound which acts as an agonist for the mechanosensitive ion channel PIEZO1, and is used in research into the function of touch perception.

References

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