Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss.
Leanne CarrottMichael R BowlCarlos AguilarStuart L JohnsonLauren ChessumMelissa WestSusan MorseJoanne DorningElizabeth SmartRachel Hardisty-HughesGreg BallAndrew ParkerAlun R BarnardRobert E MacLarenSara WellsWalter MarcottiSteve D M BrownPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
In the mammalian cochlea, the sensory inner hair cells (IHCs) encode auditory information. They do this by converting sound wave-induced mechanical motion of their hair bundles into an electrical current. This current generates a receptor potential that controls release of glutamate neurotransmitter from their ribbon synapses onto the auditory afferent fiber. We show that the synapse-enriched protein Np65, encoded by the Neuroplastin gene, is localized at the IHC presynaptic region. In mutant mice, absence of Np65 causes early-onset sensorineural hearing loss and prevents normal neurotransmitter release in IHCs and colocalization of presynaptic ribbons with postsynaptic afferents. We identified Neuroplastin as a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals.
Keyphrases
- early onset
- hearing loss
- induced apoptosis
- cell cycle arrest
- late onset
- genome wide
- copy number
- working memory
- healthcare
- oxidative stress
- high glucose
- intellectual disability
- skeletal muscle
- cell death
- gene expression
- adipose tissue
- mass spectrometry
- risk assessment
- protein protein
- pi k akt
- drug induced
- high resolution
- human health
- transcription factor