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TMHS Is an Integral Component of the Mechanotransduction Machinery of Cochlear Hair Cells
It is shown that mechanotransduction is impaired in mice lacking the tetraspan TMHS, which resembles other ion channel regulatory subunits such as the transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor regulatory proteins (TARPs) of AMPA receptors that facilitate channel transport and regulate the properties of pore-forming channel subunits. Expand
TMIE Is an Essential Component of the Mechanotransduction Machinery of Cochlear Hair Cells
It is shown that the transmembrane protein TMIE forms a ternary complex with the tip-link component PCDH15 and its binding partner TMHS/LHFPL5 and alternative splicing of the PC DH15 cytoplasmic domain regulates formation of this ternARY complex. Expand
Subunit determination of the conductance of hair-cell mechanotransducer channels
The unitary conductance of outer hair cell mechanotransducer (MT) channels was reduced relative to wild type, and the tonotopic gradient in conductance, where channels from the cochlear base are nearly twice as conducting as those at the apex, was almost absent. Expand
Harmonin Mutations Cause Mechanotransduction Defects in Cochlear Hair Cells
It is shown that the PDZ-domain protein harmonin is a component of the upper tip-link density (UTLD), where CDH23 inserts into the stereociliary membrane, and contributes to establishing the sensitivity of mechanotransduction channels to displacement. Expand
Structure of the human voltage-gated sodium channel Nav1.4 in complex with beta 1.
Voltage-gated sodium (Nav) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of aExpand
A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells
The findings suggest that DFNB12 belongs to a new class of disorder that is caused by defects in tip links, and it is proposed that mutations in other genes that cause USH1 and nonsyndromic deafness may also have distinct effects on hair cell development and function. Expand
Improved calcium sensor GCaMP-X overcomes the calcium channel perturbations induced by the calmodulin in GCaMP
The intrinsic problem prevailing over different versions and applications is unveiled, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (CaV1) and the development ofGCaMP-X is developed to overcome these limitations. Expand
Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1
The high-resolution structure of a human voltage-gated sodium channel, and the structures of an insect Nav channel bound to the toxins that cause pufferfish and shellfish poisoning in humans, give insight into the molecular basis of sodium ion permeation and provide a path toward structure-based drug discovery. Expand
Regulation of PCDH15 function in mechanosensory hair cells by alternative splicing of the cytoplasmic domain
These findings reveal an essential role for PCDH15-CD2 in the formation of kinociliary links and hair bundle polarization, and show that several PC DH15 isoforms can function redundantly at tip links. Expand
Using injectoporation to deliver genes to mechanosensory hair cells
A method termed injectoporation is described that combines tissue microinjection with electroporation to express cDNAs and shRNAs in mouse cochlear hair cells and it is compatible with the analysis of hair cell function using imaging approaches and electrophysiology. Expand