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Development of endocytosis in cochlear inner hair cells

Subject Area Otolaryngology, Phoniatrics and Audiology
Molecular Biology and Physiology of Neurons and Glial Cells
Term from 2016 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 327914803
 
Final Report Year 2022

Final Report Abstract

Mammalian inner hair cells (IHC) transduce with excellent temporal precision mechanical sound stimuli into graded receptor potentials and indefatigable transmitter release over a wide dynamic range. Before the onset of hearing, IHCs undergo terminal differentiation that includes the maturation of transmitter release that becomes more efficient and undergoes profound changes in the composition of involved molecules and the synaptic morphology. In contrast to synaptic release via vesicle exocytosis, mechanisms of compensatory endocytosis, especially of its terminal differentiation were largely unknown prior to the studies presented here. In summary, using electrophysiological membrane capacitance recordings reflecting exoand endocytosis, we here showed that the kinetics of endocytosis change upon terminal differentiation resulting in an increased efficiency of vesicle pool replenishment in mature IHCs. Moreover, the molecular composition and function of the endocytic machinery changes during terminal differentiation of IHCs, which was shown on protein level and using quantitative fluorescence in situ hybridization in the whole-mount tissue, a method that was successfully established during this funding period in our lab. Most prominently, we found an overall increase in the abundance of endocytic components indicating that increased endocytosis rates might result from a higher supply of proteins fueling endocytosis. Additionally, we identified a novel protein, Alix, as essential for hearing function. In a follow-up study funded by Saarland University, we are currently further investigation the function of Alix in the auditory system.

Publications

  • (2019) Cochlea-Specific Deletion of Cav1.3 Calcium Channels Arrests Inner Hair Cell Differentiation and Unravels Pitfalls of Conditional Mouse Models. Front Cell Neurosci, 13:225
    Eckrich S, Hecker D, Sorg K, Blum K, Fischer K, Münkner S, Wenzel G, Schick B, Engel J
    (See online at https://doi.org/10.3389/fncel.2019.00225)
  • (2021) Quantitative Fluorescent in situ Hybridization Reveals Differential Transcription Profile Sharpening of Endocytic Proteins in Cochlear Hair Cells Upon Maturation. Front Cell Neurosci
    Huang G and Eckrich S
    (See online at https://doi.org/10.3389/fncel.2021.643517)
 
 

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