We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Otoferlin acts as a Ca<sup>2+</sup> sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses.
- Authors
Michalski, Nicolas; Goutman, Juan D.; Auclair, Sarah Marie; de Monvel, Jacques Boutet; Tertrais, Margot; Emptoz, Alice; Parrin, Alexandre; Nouaille, Sylvie; Guillon, Marc; Sachse, Martin; Ciric, Danica; Bahloul, Amel; Hardelin, Jean-Pierre; Sutton, Roger Bryan; Avan, Paul; Krishnakumar, Shyam S.; Rothman, James E.; Dulon, Didier; Safieddine, Saaid; Petit, Christine
- Abstract
Hearing relies on rapid, temporally precise, and sustained neurotransmitter release at the ribbon synapses of sensory cells, the inner hair cells (IHCs). This process requires otoferlin, a six C2-domain, Ca2+-binding transmembrane protein of synaptic vesicles. To decipher the role of otoferlin in the synaptic vesicle cycle, we produced knock-in mice (Otof Ala515,Ala517/Ala515,Ala517) with lower Ca2+-binding affinity of the C²C domain. The IHC ribbon synapse structure, synaptic Ca²+ currents, and otoferlin distribution were unaffected in these mutant mice, but auditory brainstem response wave-I amplitude was reduced. Lower Ca2+ sensitivity and delay of the fast and sustained components of synaptic exocytosis were revealed by membrane capacitance measurement upon modulations of intracellular Ca2+ concentration, by varying Ca2+ influx through voltage-gated Ca2+- channels or Ca2+ uncaging. Otoferlin thus functions as a Ca2+ sensor, setting the rates of primed vesicle fusion with the presynaptic plasma membrane and synaptic vesicle pool replenishment in the IHC active zone.
- Subjects
HAIR cells; VESICLES (Cytology); AUDITORY perception; CHIMERIC proteins; SYNAPSES
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.31013.001