title: Neuroplastin Isoform Np55 Is Expressed in the Stereocilia of Outer Hair Cells and Required for Normal Outer Hair Cell Function.
abstract: Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanontransduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function.
  
  
  
  Amplification of input sound signals, which is needed for the auditory sense organ to detect sounds over a wide intensity range, depends on mechanical coupling of outer hair cells to the tectorial membrane. The current study shows that neuroplastin, a member of the Ig superfamily, which has previously been linked to the regulation of synaptic plasticity, is critical to maintain a stable mechanical link of outer hair cells with the tectorial membrane. In vivo recordings demonstrate that neuroplastin is essential for sound amplification and that mutation in neuroplastin leads to auditory impairment in mice.
authors: The Dorris Neuroscience Center, Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037.
authors: Wei-Zheng
authors: 0000-0002-1480-032X
authors: WZ
authors: Zeng
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California 94305, and.
authors: Nicolas
authors: 0000-0001-8007-9246
authors: N
authors: Grillet
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California 94305, and.
authors: James B
authors: 0000-0001-5715-9125
authors: JB
authors: Dewey
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California 94305, and.
authors: Alix
authors: A
authors: Trouillet
authors: Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239.
authors: Jocelyn F
authors: JF
authors: Krey
authors: Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239.
authors: Peter G
authors: 0000-0002-9787-5860
authors: PG
authors: Barr-Gillespie
authors: Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California 94305, and.
authors: John S
authors: JS
authors: Oghalai
authors: The Dorris Neuroscience Center, Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California 92037, umueller@scripps.edu.
authors: Ulrich
authors: 0000-0003-2736-6494
authors: U
authors: Müller
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000166:cytology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D009154:Mutation / Q000235:genetics; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D059547:Stereocilia / Q000502:physiology* / Q000648:ultrastructure; D041623:Tomography, Optical Coherence; D014161:Transduction, Genetic
chemical_list: D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C577174:neuroplastin protein, mouse
keywords: amplification; deafness; hair cells; inner ear; neuroplastin; tectorial membrane