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The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing
Author(s) -
Vogl Christian,
Butola Tanvi,
Haag Natja,
Hausrat Torben J,
Leitner Michael G,
Moutschen Michel,
Lefèbvre Philippe P,
Speckmann Carsten,
Garrett Lillian,
Becker Lore,
Fuchs Helmut,
Hrabe de Angelis Martin,
Nietzsche Sandor,
Kessels Michael M,
Oliver Dominik,
Kneussel Matthias,
Kilimann Manfred W,
Strenzke Nicola
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643689
Subject(s) - german , library science , medicine , history , computer science , archaeology
Lipopolysaccharide‐responsive beige‐like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain‐containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week. LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia. Our data suggest that due to the loss of structural integrity of the central parts of the hair bundle, the hair cell receptor potential is reduced, resulting in a loss of cochlear sensitivity and functional loss of the fraction of spiral ganglion neurons with low spontaneous firing rates. Clinical data obtained from two human patients with protein‐truncating nonsense or frameshift mutations suggest that LRBA deficiency may likewise cause syndromic sensorineural hearing impairment in humans, albeit less severe than in our mouse model.