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Sci Rep. 2019 Oct 3;9(1):14273. doi: 10.1038/s41598-019-50710-2.

Otoferlin Depletion Results in Abnormal Synaptic Ribbons and Altered Intracellular Calcium Levels in Zebrafish.

Author information

1
Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon, USA.
2
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA.
3
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA.
4
National Institute of Deafness and Other Communication Disorders (NIDCD), NIH, Maryland, USA.
5
Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon, USA. colin.johnson@oregonstate.edu.
6
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA. colin.johnson@oregonstate.edu.

Abstract

The protein otoferlin plays an essential role at the sensory hair cell synapse. Mutations in otoferlin result in deafness and depending on the species, mild to strong vestibular deficits. While studies in mouse models suggest a role for otoferlin in synaptic vesicle exocytosis and endocytosis, it is unclear whether these functions are conserved across species. To address this question, we characterized the impact of otoferlin depletion in zebrafish larvae and found defects in synaptic vesicle recycling, abnormal synaptic ribbons, and higher resting calcium concentrations in hair cells. We also observed abnormal expression of the calcium binding hair cell genes s100s and parvalbumin, as well as the nogo related proteins rtn4rl2a and rtn4rl2b. Exogenous otoferlin partially restored expression of genes affected by endogenous otoferlin depletion. Our results suggest that in addition to vesicle recycling, depletion of otoferlin disrupts resting calcium levels, alters synaptic ribbon architecture, and perturbs transcription of hair cells specific genes during zebrafish development.

PMID:
31582816
DOI:
10.1038/s41598-019-50710-2
Free PMC Article

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