PIEZO1: A Mechanosensitive Ion Channel Protein

Thu, 09/19/2013 - 16:10

PIEZO1, and its close homologue PIEZO2, are mechanosensitive ion channel proteins. Mechanosensitive ion channels couple protein conformation to the mechanics of the surrounding membrane, and switch between a closed state and an open state in response to changes in membrane tension, thickness, or curvature. Cells use this information to ensure viability under conditions of osmotic stress or membrane deformation (1).

PIEZO1, also known as FAM38A, is a large (2521 amino acid, 287kDa) protein with multiple transmembrane domains, and bears little resemblance to other ion channel proteins. Using GFP fusion constructs of ion channels with known stoichiometry, Coste et al have shown that PIEZO1 assembles as a homo-tetramer in living cells. This same group used PIEZO1 antibodies to generate Western blot data to support this observation and, additionally, demonstrated that PIEZO1 is not associated with other pore-forming proteins (2).

Expression levels of PIEZO1 are highest in lung, bladder and skin (3). PIEZO channels can be inhibited by Ruthenium Red, a non-specific inhibitor of many cation channels, and are also inhibited by GsMTx4, a more specific inhibitor of cationic mechanosensitive ion channels.

Two mutations in PIEZO1 have been identified which slow inactivation of the ion channel. These are implicated in hereditary xerocytosis (HX), an autosomal dominant condition that gives rise to a form of haemolytic anaemia which occurs as a result of erythrocyte dehydration following cellular efflux of potassium and water (4).

Immunocytochemistry/Immunofluorescence: PIEZO1 Antibody Immunocytochemistry/Immunofluorescence: PIEZO1 Antibody

During integrin-dependent migration, cells use the traction produced by integrin binding to the extracellular matrix for motility. McHugh et al have shown that depletion of PIEZO1 expression dramatically reduces the affinity of cells for beta 1 integrin, which subsequently reduces cell adhesion. This reduction in PIEZO1 expression can cause increased cell migration and metastasis in small cell lung cancer lines, as the cells become anchorage independent and instead use the actin cytoskeleton to push their way through the extracellular matrix. This group used PIEZO1 antibodies to illustrate actin rearrangement in PIEZO1-depleted cells by immunocytochemistry (5).

  1. PMID: 22000509
  2. PMID: 22343900
  3. PMID: 22790400
  4. PMID: 23972840
  5. PMID: 22792288

Novus Biologicals offers various PIEZO1 reagents for your research needs including:

Written by Emma Easthope

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