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Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cellsPangršič, Tina ...Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an ... aspartate to glycine substitution in the C2F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca2+ signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We concludethat replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles.Source: Nature neuroscience. - ISSN 1097-6256 (Letn. 13, št. 7, 2010, str. 869-876)Type of material - article, component partPublish date - 2010Language - englishCOBISS.SI-ID - 27428569
Author
Pangršič, Tina |
Lasarow, Livia |
Reuter, Kirsten |
Takago, Hideki
Topics
Hair Cells, Inner |
Auditory Perception |
Spiral Ganglion |
Acoustic Stimulation |
Synaptic Vesicles |
Calcium |
Exocytosis |
Deafness |
Synaptic Transmission |
Patch-Clamp Techniques |
Neurotransmitters |
Disease Models, Animal |
Mice, Inbred Strains |
Sinaptični mešički |
Sluh, zaznava |
Akustična stimulacija |
Dlakaste celice notranje |
Spiralni ganglij |
Eksocitoza |
Nevrotransmiterji |
Bolezen, živalski modeli |
Sinaptični prenos |
Kalcij |
Snov-vnos, tehnike |
Miši, čiste linije |
Gluhost
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Pangršič, Tina | 23346 |
Lasarow, Livia | ![]() |
Reuter, Kirsten | ![]() |
Takago, Hideki | ![]() |
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