Abstract
We show that a cage-shaped F-actin network is essential for maintaining a tight spatial organization of Cav1.3 Ca(2+) channels at the synaptic ribbons of auditory inner hair cells. This F-actin network is also found to provide mechanosensitivity to the Cav1.3 channels when varying intracellular hydrostatic pressure. Furthermore, this F-actin mesh network attached to the synaptic ribbons directly influences the efficiency of otoferlin-dependent exocytosis and its sensitivity to intracellular hydrostatic pressure, independently of its action on the Cav1.3 channels. We propose a new mechanistic model for vesicle exocytosis in auditory hair cells where the rate of vesicle recruitment to the ribbons is directly controlled by a synaptic F-actin network and changes in intracellular hydrostatic pressure.
Highlights
Auditory hair cells convert tiny variations of sound pressure through the displacement of their apical hair bundles into analogous voltage waveforms. Neural encoding of these microphonic potentials occurs at the ribbon synapses of inner hair cells (IHCs) by mechanisms involving Cav1.3 channels (Platzer et al, 2000; Brandt et al, 2003; Brandt et al, 2005) and otoferlin-dependent exocytosis of synaptic vesicles (Roux et al, 2006; Beurg et al, 2010, Vincent et al, 2014)
We investigated whether F-actin and intracellular hydrostatic pressure regulate synaptic exocytosis in mouse IHCs
Considering that a 40 nm diameter synaptic vesicle corresponds to 37 aF (Lenzi et al, 1999), we estimated a RRP size of about 590 vesicles, i.e 33 vesicles per ribbons if we assume a number of 18 ribbons per IHCs
Summary
Auditory hair cells convert tiny variations of sound pressure through the displacement of their apical hair bundles into analogous voltage waveforms Neural encoding of these microphonic potentials occurs at the ribbon synapses of inner hair cells (IHCs) by mechanisms involving Cav1.3 channels (Platzer et al, 2000; Brandt et al, 2003; Brandt et al, 2005) and otoferlin-dependent exocytosis of synaptic vesicles (Roux et al, 2006; Beurg et al, 2010, Vincent et al, 2014). Vincent et al show that in hair cells, a cage-like network made from a protein called actin surrounds each active zone. This network helps to position the calcium ion channels. We investigated whether F-actin and intracellular hydrostatic pressure regulate synaptic exocytosis in mouse IHCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
