Calcium- and Otoferlin-Dependent Exocytosis by Immature Outer Hair Cells

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Calcium- and otoferlin-dependent exocytosis by immature outer hair cells.

Immature cochlear outer hair cells (OHCs) make transient synaptic contacts (ribbon synapses) with type I afferent nerve fibers, but direct evidence of synaptic vesicle exocytosis is still missing. We thus investigated calcium-dependent exocytosis in murine OHCs at postnatal day 2 (P2)-P3, a developmental stage when calcium current maximum amplitude was the highest. By using time-resolved patch-...

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A synaptic F-actin network controls otoferlin-dependent exocytosis in auditory inner hair cells

We show that a cage-shaped F-actin network is essential for maintaining a tight spatial organization of Cav1.3 Ca(2+) channels at the synaptic ribbons of auditory inner hair cells. This F-actin network is also found to provide mechanosensitivity to the Cav1.3 channels when varying intracellular hydrostatic pressure. Furthermore, this F-actin mesh network attached to the synaptic ribbons directl...

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Control of exocytosis by synaptotagmins and otoferlin in auditory hair cells.

In pre-hearing mice, vesicle exocytosis at cochlear inner hair cell (IHC) ribbon synapses is triggered by spontaneous Ca(2+) spikes. At the onset of hearing, IHC exocytosis is then exclusively driven by graded potentials, and is characterized by higher Ca(2+) efficiency and improved synchronization of vesicular release. The molecular players involved in this transition are still unknown. Here w...

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Otoferlin is critical for a highly sensitive and linear calcium-dependent exocytosis at vestibular hair cell ribbon synapses.

Otoferlin, a C2-domain-containing Ca(2+) binding protein, is required for synaptic exocytosis in auditory hair cells. However, its exact role remains essentially unknown. Intriguingly enough, no balance defect has been observed in otoferlin-deficient (Otof(-/-)) mice. Here, we show that the vestibular nerve compound action potentials evoked during transient linear acceleration ramps in Otof(-/-...

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Calcium Regulates Molecular Interactions of Otoferlin with SNARE Proteins Required for Hair Cell Exocytosis

Background: Otoferlin deficiency impairs haircell exocytosis and causes deafness. Results: Otoferlin binds Ca, regulating phosphatidylinositol 4,5-bisphosphate, t-SNARE, and intramolecular C2 interactions; otoferlin directly interacts with SNAP-25 and syntaxin-1B. Conclusion: Low Ca promotes interactions between otoferlin C2C, C2D, C2E, and C2F; high Ca drives t-SNARE and lipid interactions. Si...

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ژورنال

عنوان ژورنال: Journal of Neuroscience

سال: 2008

ISSN: 0270-6474,1529-2401

DOI: 10.1523/jneurosci.4653-07.2008