This guide focuses on the molecular mechanism of otoferlin-mediated vesicle docking and Ca 2+raised to the 2 plus power sensing in inner hair cells (IHCs). Role: Otoferlin acts as a key Ca 2+raised to the 2 plus power sensor for synaptic vesicle fusion in auditory IHCs.
It tethers vesicles to the plasma membrane, facilitating sound encoding.
This molecular mechanism allows the ear to convert sound into neural signals at incredibly high speeds. tm,cc,jp
Sensing: The C2D domain is identified as critical, as disruptions in this area alter synaptic sound encoding.
Lack of functional otoferlin or its C2 domain interaction prevents proper vesicle docking, leading to profound deafness. Summary Table: Otoferlin C2 Interactions Function/Location C2B-C2G Main interface for membrane binding C2D Crucial Ca 2+raised to the 2 plus power binding site; mutations affect sound encoding C2F-C2G Rearrange upon membrane binding to close structure Target Membrane Membrane where vesicles are docked This guide focuses on the molecular mechanism of
The study highlights that membrane binding involves a cooperative effort of multiple domains.
Otoferlin engages the target membrane specifically through a large interface involving the N-terminal C2B and C-terminal C2F-C2G domains . Ca 2+raised to the 2 plus power This molecular mechanism allows the ear to convert
The binding requires cooperation between multiple C2 domains to secure the vesicle to the target membrane.