| PIEZO1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
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]
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]
Antagonists
Perforin-1 Perforin (PRF), encoded by the PRF1 gene, is a pore-forming toxin housed in the secretory granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Together, these cells are known as cytotoxic lymphocytes (CLs).
Hereditary stomatocytosis describes a number of inherited, mostly autosomal dominant human conditions which affect the red blood cell and create the appearance of a slit-like area of central pallor (stomatocyte) among erythrocytes on peripheral blood smear. The erythrocytes' cell membranes may abnormally 'leak' sodium and/or potassium ions, causing abnormalities in cell volume. Hereditary stomatocytosis should be distinguished from acquired causes of stomatocytosis, including dilantin toxicity and alcoholism, as well as artifact from the process of preparing peripheral blood smears.
NLR family pyrin domain containing 3 (NLRP3), is a protein that in humans is encoded by the NLRP3 gene located on the long arm of chromosome 1.
Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments.
Large conductance mechanosensitive ion channels (MscLs) (TC# 1.A.22) are a family of pore-forming membrane proteins that are responsible for translating stresses at the cell membrane into an electrophysiological response. MscL has a relatively large conductance, 3 nS, making it permeable to ions, water, and small proteins when opened. MscL acts as stretch-activated osmotic release valve in response to osmotic shock.
CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the CD59 gene. It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxin protein family.
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene. KCNK4 protein channels are also called TRAAK channels.
Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the PBRM1 gene.
Triggering receptor expressed on myeloid cells 2(TREM2) is a protein that in humans is encoded by the TREM2 gene. TREM2 is expressed on macrophages, immature monocyte-derived dendritic cells, osteoclasts, and microglia, which are immune cells in the central nervous system. In the liver, TREM2 is expressed by several cell types, including macrophages, that respond to injury. In the intestine, TREM2 is expressed by myeloid-derived dendritic cells and macrophage. TREM2 is overexpressed in many tumor types and has anti-inflammatory activities. It might therefore be a good therapeutic target.
Mucolipin-3 also known as TRPML3 is a protein that in humans is encoded by the MCOLN3 gene. It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.
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.
Mechanosensitive channels (MSCs), mechanosensitive ion channels or stretch-gated ion channels are membrane proteins capable of responding to mechanical stress over a wide dynamic range of external mechanical stimuli. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They are the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst). The channels vary in selectivity for the permeating ions from nonselective between anions and cations in bacteria, to cation selective allowing passage Ca2+, K+ and Na+ in eukaryotes, and highly selective K+ channels in bacteria and eukaryotes.
Pannexin 1 is a protein in humans that is encoded by the PANX1 gene.
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.
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.
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.
Grammostola mechanotoxin #4, also known as M-theraphotoxin-Gr1a (M-TRTX-Gr1a), is a neurotoxin isolated from the venom of the spider Chilean rose tarantula Grammostola spatulate. This amphiphilic peptide, which consists of 35 amino acids, belongs to the inhibitory cysteine knot (ICK) peptide family. It reduces mechanical sensation by inhibiting mechanosensitive channels (MSCs).
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.
