The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses

doi:10.1016/j.isci.2022.105628

iScience

Volume 25, Issue 12, 22 December 2022, 105628

https://doi.org/10.1016/j.isci.2022.105628 Get rights and content

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open access

Highlights

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The inner hair cell (IHC), the genuine auditory sensory cell, expresses SNAP-25
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IHC targeted deletion of SNAP-25 leads to deafness and synaptic degeneration
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Without SNAP-25, the IHC transmitter release is drastically reduced
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Viral transfer of SNAP-25 cDNA rescues hearing and prevents synaptic degeneration

Summary

Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has so far remained controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generating and analyzing a conditional knockout mouse model allowing a targeted postnatal deletion of Snap-25 in IHCs. Mice subjected to IHC Snap-25 inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of Snap-25 in these mutant mice rescued their hearing function by restoring IHC exocytosis and preventing synapses and hair cells from degeneration. These results demonstrate that SNAP-25 is essential for normal hearing function, most likely by ensuring IHC exocytosis and ribbon synapse maintenance.

Graphical abstract

Subject areas

Biological sciences

Neuroscience

Sensory neuroscience

Data and code availability

All data reported in this paper is available from the lead contact upon request. Of note, deep sequencing data we provide here concerns only the neuronal SNAREs and proteins essential for IHC synaptic transmission, which is the scope of the article. These data represent only a small fraction of a bigger deep sequencing dataset that is currently being analyzed and will be the subject of a separate publication.
This paper does not report original code.
Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request.

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⁹: Lead contact