Article (Scientific journals)
The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing
Vogl, C.; Butola, T.; Haag, N. et al.
2017In EMBO Reports, 18 (11), p. 2015-2029
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Keywords :
Article; Corti organ
Abstract :
[en] 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. © 2017 The Authors.
Disciplines :
Otolaryngology
Author, co-author :
Vogl, C.;  Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany
Butola, T.;  Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany, Synaptic Nanophysiology Group, Max-Planck-Institute for Biophysical Chemistry Göttingen, Göttingen, Germany
Haag, N.;  Institute for Biochemistry I, University Hospital Jena, Jena, Germany, Institute of Human Genetics, University Hospital RWTH Aachen, Aachen, Germany
Hausrat, T. J.;  Department for Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Leitner, M. G.;  Department of Physiology, Philipps University Marburg, Marburg, Germany
Moutschen, Michel  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Lefèbvre, Philippe ;  Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie
Speckmann, C.;  Division of Pediatric Hematology and Oncology, Center for Chronic Immunodeficiency and Department of Pediatrics and Adolescent Medicine, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Garrett, L.;  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Becker, L.;  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Fuchs, H.;  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Hrabe de Angelis, M.;  German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München, München, Germany, German Center for Diabetes Research (DZD), Neuherberg, Germany
Nietzsche, S.;  Department of Anatomy, University Hospital Jena, Jena, Germany
Kessels, Maurijn ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Oliver, D.;  Department of Physiology, Philipps University Marburg, Marburg, Germany
Kneussel, M.;  Department for Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Kilimann, M. W.;  Institute for Auditory Neuroscience, University Medical Center Göttingen, Göttingen, Germany, Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Göttingen, Germany
Strenzke, N.;  Auditory Systems Physiology Group, Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany
More authors (8 more) Less
Language :
English
Title :
The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing
Publication date :
2017
Journal title :
EMBO Reports
ISSN :
1469-221X
eISSN :
1469-3178
Publisher :
Wiley-VCH Verlag
Volume :
18
Issue :
11
Pages :
2015-2029
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Grant STR 1027/2 in Priority Program 1608 and project A6 in the Collaborative Research Center 889
Funders :
DFG - Deutsche Forschungsgemeinschaft [DE]
Sverige Vetenskapsrådet [SE]
German Federal Ministry of Education and Research
Elisabeth und Helmut Uhl Foundation
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