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Journal articles
The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells
Abstract : Protocadherin-15 (Pcdh15) is a component of the tip-links, the extracellular filaments that gate hair cell mechano-electrical transduction channels in the inner ear. There are three Pcdh15 splice isoforms (CD1, CD2 and CD3), which only differ by their cyto-plasmic domains; they are thought to function redundantly in mechano-electrical transduction during hair-bundle development, but whether any of these isoforms composes the tip-link in mature hair cells remains unknown. By immunolabelling and both morphological and electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15 ex38-fl/ex38-fl Myo15-cre +/À) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential component of tip-links in mature auditory hair cells. The finding, in the homozygous or compound heterozygous state, of a PCDH15 frameshift mutation (p.P1515Tfs*4) that affects only Pcdh15-CD2, in profoundly deaf children from two unrelated families, extends this conclusion to humans. These results provide key information for identification of new components of the mature auditory mechano-electrical trans-duction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects.
Cited literature [21 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01237053
Contributor : Christine Petit <>
Submitted on : Wednesday, December 2, 2015 - 4:10:35 PM
Last modification on : Wednesday, October 14, 2020 - 3:40:24 AM
Long-term archiving on: : Thursday, March 3, 2016 - 1:33:49 PM
Contributor : Christine Petit <>
Submitted on : Wednesday, December 2, 2015 - 4:10:35 PM
Last modification on : Wednesday, October 14, 2020 - 3:40:24 AM
Long-term archiving on: : Thursday, March 3, 2016 - 1:33:49 PM
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Pepermans et al EMBO MolMed201...
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