The conversion of force into an electrical cellular signal is mediated by the opening of different types of mechanosensitive ion channels (MSCs), including TREK/TRAAK K channels, Piezo1/2, TMEM63/OSCA, and TMC1/2. Mechanoelectrical transduction plays a key role in hearing, balance, touch, and proprioception and is also implicated in the autonomic regulation of blood pressure and breathing. Thus, dysfunction of MSCs is associated with a variety of inherited and acquired disease states. Significant progress has recently been made in identifying these channels, solving their structure, and understanding the gating of both hyperpolarizing and depolarizing MSCs. Besides prototypical activation by membrane tension, additional gating mechanisms involving channel curvature and/or tethered elements are at play.
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http://dx.doi.org/10.1016/j.cell.2019.08.049 | DOI Listing |
Front Neurol
December 2024
Department of Physiology, University of Kentucky, Lexington, KY, United States.
Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter 'transducing' stereocilia.
View Article and Find Full Text PDFElife
January 2025
Department of Otorhinolaryngology - Head & Neck Surgery, University of Maryland School of Medicine, Baltimore, United States.
Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechano-electrical transduction (MET) apparatus. These interactions have been proposed to be functionally relevant across mechanosensory organs and vertebrate species. Here, we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line.
View Article and Find Full Text PDFNat Commun
January 2025
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Glioblastoma (GBM) is a malignant brain tumor with diffuse infiltration. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 for confined migration through restricted space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal endocytic vesicle accumulation at cell front and filamentous actin assembly at cell rear in a polarized manner.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
School of Biosciences, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Myosin-VIIA (MYO7A) is an unconventional myosin responsible for syndromic (Usher 1B) or nonsyndromic forms of deafness in humans when mutated. In the cochlea, MYO7A is expressed in hair cells, where it is believed to act as the motor protein tensioning the mechanoelectrical transducer (MET) channels, thus setting their resting open probability (). However, direct evidence for this unique role for an unconventional myosin in mature hair cells is lacking.
View Article and Find Full Text PDFNeuron
December 2024
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China; Department of Neurobiology, School of Basic Medicine, Capital Medical University, Beijing, China; Institute for Medical Physiology, Chinese Institutes for Medical Research, Beijing, China. Electronic address:
Mammalian transmembrane channel-like proteins 1 and 2 (TMC1 and TMC2) have emerged as very promising candidate mechanotransduction channels in hair cells. However, controversy persists because the heterogeneously expressed TMC1/2 in cultured cells lack evidence of mechanical gating, primarily due to their absence from the plasma membrane. By employing domain swapping with OSCA1.
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