Unconventional molecular regulation of synaptic vesicle replenishment in cochlear inner hair cells

• DOI: 10.1242/jcs.162099
• Publication Date: 2015-01-22T04:00:46Z
• Authors: Christian Vogl; Benjamin H. Cooper; Jakob Neef; Sonja M. Wojcik; Kerstin Reim; Ellen Reisinger; Nils Brose; Jeong-Seop Rhee; Tobias Moser; Carolin Wichmann
• Keywords: Active zone; Ribbon synapse; Munc-18; Secretory Vesicle; Kiss-and-run fusion

Ribbon synapses of cochlear inner hair cells (IHCs) employ efficient vesicle replenishment to indefatigably encode sound. In neurons, neuroendocrine and immune cells, depends on proteins the mammalian uncoordinated 13 (Munc13) Ca2+-dependent activator for secretion (CAPS) families, which prime vesicles exocytosis. Here, we tested whether Munc13 CAPS also regulate exocytosis in mouse IHCs by combining immunohistochemistry with auditory systems physiology IHC patch-clamp recordings mice lacking isoforms. Surprisingly, did not detect or at presynaptic active zones (AZs) found normal as well brainstem responses (ABRs) deletion mutants. Instead, show that otoferlin, a C2-domain protein critical vesicular fusion IHCs, clusters plasma membrane AZ. Electron tomography otoferlin-deficient revealed reduction short tethers holding AZ, might be structural correlate impaired priming IHCs. We conclude use an unconventional machinery involves otoferlin.