Entwicklung der Endozytose in inneren Haarzellen der Cochlea
Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Zusammenfassung der Projektergebnisse
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.
Projektbezogene Publikationen (Auswahl)
- (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
(Siehe online unter 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
(Siehe online unter https://doi.org/10.3389/fncel.2021.643517)
