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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells
EMBO Molecular Medicine, Volume 6, No. 7, Year 2014
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Description
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 cytoplasmic 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 (Pcdh15ex38-fl/ex38-fl Myo15-cre+/-) 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 transduction machinery. This will also serve as a basis for the development of gene therapy for deafness caused by PCDH15 defects. © 2014.
Authors & Co-Authors
Pepermans, Elise
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
Michel, Vincent
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
Goodyear, Richard
United Kingdom, Brighton
University of Sussex
Bonnet, Crystel
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Institut de la Vision
Abdi, Samia
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
Dupont, Typhaine
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
Gherbi, Souad
France, Paris
Hôpital Necker Enfants Malades
Holder, Muriel
France, Lille
Chu Lille
Makrelouf, Mohamed
Algeria, Algiers
Université D’alger 1
Hardelin, Jean Pierre
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
Marlin, Sandrine
France, Paris
Hôpital Necker Enfants Malades
Zenati, Akila
Algeria, Algiers
Université D’alger 1
Richardson, Guy
United Kingdom, Brighton
University of Sussex
Avan, Paul
France, Clermont-ferrand
Université Clermont Auvergne
France, Paris
Inserm
France, Clermont-ferrand
Centre Jean Perrin
Bahloul, Amel
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
Petit, Christine
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Institut de la Vision
France, Paris
Collège de
Statistics
Citations: 53
Authors: 16
Affiliations: 12
Identifiers
Doi:
10.15252/emmm.201403976
ISSN:
17574676
e-ISSN:
17574684
Research Areas
Cancer
Disability
Genetics And Genomics
Maternal And Child Health