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

Abstract

ABSTRACT

Axial tubule junctions control rapid calcium signaling in atria

“…AT and TT structures and isolated AM were preserved by high-pressure freezing with an HPM100 system (Leica) as described previously (51). ET at the Electron Microscopy core facility at the European Molecular Biology Laboratory (EMBL) Heidelberg (Heidelberg, Germany) and at the EM services of the University of Colorado Boulder (Boulder, Colorado, USA) was performed as described previously (23).…”

Molecularly and structurally distinct synapses mediate reliable encoding and processing of auditory information

“…IHC synapses substantially depart from the more conventional molecular composition of calyceal synapses of the auditory pathway heavily building on the multi C 2 domain protein otoferlin (Roux et al, 2006;Pangrsic et al, 2010;Vogl et al, 2015). Its importance in hearing and the resulting synaptopathy will be part of the next section.…”

“…At least two separate modes of endocytosis are observed at IHC ribbon synapses: (i) clathrin-mediated endocytosis, which is taking place mainly under normal stimulation and (ii) bulk endocytosis, to compensate large membrane turnover at high release rates . Multiple mechanism(s) of exocytosis at ribbon synapses suggestions have been made including the conveyor belt model and homotypic fusion events of vesicles at the ribbon or 2-dimensional diffusion of vesicles on the surface of the ribbon (Bunt, 1971;von Gersdorff, 2001;Glowatzki and Fuchs, 2002;Parsons and Sterling, 2003;Neef et al, 2007;Snellman et al, 2011;Graydon et al, 2014). IHC ribbon synapses have to be capable of detecting and conveying different sound pressure levels and this with highest temporal precision.…”

“…The RRP was initially defined at hippocampal neurons as those quanta that are released during the transient burst of exocytotic activity following application of hypertonic solution (Rosenmund and Stevens, 1996). At IHC ribbon synapses membrane-proximal vesicles are lined up next to the anchoring site of the ribbons, the presynaptic density, as it was observed in ultrastructural 3D reconstructions (Sobkowicz et al, 1982;Frank et al, 2010;Wong et al, 2014;Vogl et al, 2015; scheme in Fig. 1D) that entails a close proximity of RRP vesicles to Ca 2þ channels.…”

“…Likewise, the related priming factor CAPS (Ca 2þ -dependent activator of protein secretion) was shown to be expressed at the calyx (Kreft et al, 2003). In contrast, genetic ablation of Munc13-1/2 or CAPS1/2 does not affect synaptic transmission in IHCs (Vogl et al, 2015).…”