Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis

Ellen Reisinger, Chris Bresee, Jakob Neef, Ramya Nair, Kirsten Reuter, Anna Bulankina, Régis Nouvian, Manuel Koch, Johanna Bückers, Lars Kastrup, Isabelle Roux, Christine Petit, Stefan W. Hell, Nils Brose, Jeong Seop Rhee, Sebastian Kügler, John Brigande, Tobias Moser

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Abstract

Cochlear inner hair cells (IHCs) use Ca2+-dependent exocytosis of glutamate to signal sound information. Otoferlin (Otof), aC2 domain protein essential for IHC exocytosis and hearing, may serve as a Ca2+ sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca2+ sensors synaptotagmin 1 (Syt1) and Syt2. Support for the Ca2+ sensor of fusion hypothesis for otoferlin function comes from biochemical experiments, but additional roles in late exocytosis upstream of fusion have been indicated by physiological studies. Here, we tested the functional equivalence of otoferlin and Syt1 in three neurosecretory model systems: auditory IHCs, adrenal chromaffin cells, and hippocampal neurons. Long-term and short-term ectopic expression of Syt1 in IHCs of Otof +/+ mice by viral gene transfer in the embryonic inner ear and organotypic culture failed to rescue their Ca2+ influx-triggered exocytosis. Conversely, virally mediated overexpression of otoferlin did not restore phasic exocytosis in Syt1-deficient chromaffin cells or neurons but enhanced asynchronous release in the latter. We further tested exocytosis in Otof -/-hippocampal neurons and in Syt1-/- IHCs but found no deficits in vesicle fusion. Expression analysis of different synaptotagminisoforms indicated that Syt1andSyt2 are bsentfrommatureIHCs.Ourdata argue againstasimple functional equivalence of the two C2 domain proteins in exocytosis of IHC ribbon synapses, chromaffin cells, and hippocampal synapses.

Original languageEnglish (US)
Pages (from-to)4886-4895
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number13
DOIs
StatePublished - Mar 30 2011

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Inner Auditory Hair Cells
Synaptotagmin I
Exocytosis
Chromaffin Cells
Neurons
Synapses
Neurosecretory Systems
Viral Genes
Inner Ear
Hearing
Glutamic Acid

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reisinger, E., Bresee, C., Neef, J., Nair, R., Reuter, K., Bulankina, A., ... Moser, T. (2011). Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis. Journal of Neuroscience, 31(13), 4886-4895. https://doi.org/10.1523/JNEUROSCI.5122-10.2011

Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis. / Reisinger, Ellen; Bresee, Chris; Neef, Jakob; Nair, Ramya; Reuter, Kirsten; Bulankina, Anna; Nouvian, Régis; Koch, Manuel; Bückers, Johanna; Kastrup, Lars; Roux, Isabelle; Petit, Christine; Hell, Stefan W.; Brose, Nils; Rhee, Jeong Seop; Kügler, Sebastian; Brigande, John; Moser, Tobias.

In: Journal of Neuroscience, Vol. 31, No. 13, 30.03.2011, p. 4886-4895.

Research output: Contribution to journalArticle

Reisinger, E, Bresee, C, Neef, J, Nair, R, Reuter, K, Bulankina, A, Nouvian, R, Koch, M, Bückers, J, Kastrup, L, Roux, I, Petit, C, Hell, SW, Brose, N, Rhee, JS, Kügler, S, Brigande, J & Moser, T 2011, 'Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis', Journal of Neuroscience, vol. 31, no. 13, pp. 4886-4895. https://doi.org/10.1523/JNEUROSCI.5122-10.2011
Reisinger E, Bresee C, Neef J, Nair R, Reuter K, Bulankina A et al. Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis. Journal of Neuroscience. 2011 Mar 30;31(13):4886-4895. https://doi.org/10.1523/JNEUROSCI.5122-10.2011
Reisinger, Ellen ; Bresee, Chris ; Neef, Jakob ; Nair, Ramya ; Reuter, Kirsten ; Bulankina, Anna ; Nouvian, Régis ; Koch, Manuel ; Bückers, Johanna ; Kastrup, Lars ; Roux, Isabelle ; Petit, Christine ; Hell, Stefan W. ; Brose, Nils ; Rhee, Jeong Seop ; Kügler, Sebastian ; Brigande, John ; Moser, Tobias. / Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 13. pp. 4886-4895.
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AU - Petit, Christine

AU - Hell, Stefan W.

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