Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss
| Autor: | Susan Morse, Elizabeth Smart, Robert E MacLaren, Sara Wells, Alun R. Barnard, Michael R. Bowl, Lauren Chessum, Andrew Parker, Stuart L. Johnson, Rachel E. Hardisty-Hughes, Walter Marcotti, Joanne Dorning, Melissa West, Carlos Aguilar, Leanne Carrott, Steve D. M. Brown, Greg Ball |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Neurogenesis Receptor potential Synaptogenesis Sound perception Deafness Ribbon synapse Biology Mice 03 medical and health sciences 0302 clinical medicine Postsynaptic potential otorhinolaryngologic diseases medicine Animals Cochlea Mice Knockout Hair Cells Auditory Inner Membrane Glycoproteins General Neuroscience Articles medicine.disease Mice Inbred C57BL 030104 developmental biology Synapses Female Sensorineural hearing loss sense organs Neuroplastin Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Neuroscience. 36:222-234 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1808-15.2016 |
| Popis: | TheNeuroplastingene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutantpitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced inpitchmutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals.SIGNIFICANCE STATEMENTIn 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 theNeuroplastingene, 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 identifiedNeuroplastinas a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals. |
| Databáze: | OpenAIRE |
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