Piezo1 is a

mechanosensitive ion channel Mechanosensitive channels, mechanosensitive ion channels or stretch-gated ion channels (not to be confused with mechanoreceptors). They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They ...

protein that in humans is encoded by the gene ''PIEZO1''. Piezo1 and its close homolog

Piezo2 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. Function Piezos are ...

were cloned in 2010, using an

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...

-based screen for mechanosensitive ion channels.

Structure and function

PIEZO1 (this gene) and

PIEZO2 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. Function Piezos are ...

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 domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bil ...

s, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

s, but a more recent study by the same lab convincingly demonstrated that indeed piezo1 is the pore-forming subunit of a mechanosensitive channel. This new "PIEZO" family is catalogued as and TCDB . PIEZO1 homologues are found in ''

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

'' and ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

'', which, like other invertebrates, have a single piezo protein. It is known () that Piezo1 channel is a three-bladed propeller-like structure. A lever-like mechanogating mechanism is assumed.

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 A dorsal root ganglion (or spinal ganglion; also known as a posterior root ganglion) is a cluster of neurons (a ganglion) in a dorsal root of a spinal nerve. The cell bodies of sensory neurons known as first-order neurons are located in the do ...

, piezo1 is not expressed in sensory neurons.

Clinical significance

Piezo1 is also found in

red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...

, and gain of function mutations in the channels are associated with hereditary xerocytosis or

stomatocytosis 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 bl ...

. Piezo1 channels are pivotal integrators in vascular biology. An allele of Piezo1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...

. This allele has been demonstrated

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

to prevent cerebral malaria infection. Piezo1 has been implicated in extrusion of

epidermal cells The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...

when a layer becomes too confluent to preserve normal skin

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

. This acts to prevent excess proliferation of skin tissue, and has been implicated in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

biology as a contributing factor to

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

by assisting living cells in escaping from a

monolayer A monolayer is a single, closely packed layer of atoms, molecules, or cells. In some cases it is referred to as a self-assembled monolayer. Monolayers of layered crystals like graphene and molybdenum disulfide are generally called 2D materials. ...

. Expression of murine PIEZO1 in mouse

innate immune cell A non-specific immune cell is an immune cell (such as a macrophage, neutrophil, or dendritic cell) that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. ...

s 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 ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...

''.

Ligands

; Agonists * Jedi1/2 *

Yoda1 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 Red blood cells (RBCs), also referred to as red cells, ...

(small molecule agonist) Antagonists * Gadolinium * Streptomycin * Ruthenium Red * GsMTx4 * Dooku1

References

Transmembrane proteins {{protein-stub