Evaluation of the dynamics of microtubules for the development and maintenance of the organ of Corti and the auditory neurons

• Applicant: Professor Dr. Kristen Rak
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Otolaryngology, Phoniatrics and Audiology
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 401164334

Microtubules (MT) are essential components of the cytoskeleton and ensure the maintenance of the cellular structure, cell division and intracellular transport. While the basic structure of MT is largely conserved, they can consist of different tubulin isotypes or have a variety of post-translational modifications (PTMs). The distribution of isotypes, PTMs and other proteins, that modulate MT dynamics, is cell type specific in the organ of Corti and the auditory neurons, indicating specific functions of MT there. In addition, there is preliminary data showing a correlation between altered MT dynamics and hearing loss. The function of MT in the cells of the organ of Corti and the auditory neurons is not fully understood, but the specific expression and dynamics may play a role in the development and maintenance of the cellular function. From these findings and hypotheses, the aim of the project was derived, which the evaluation of the influence of altered MT dynamics on the development and maintenance of the organ of Corti and the auditory neurons. In order to investigate this, two questions are to be addressed and different animal models used. 1) Do changes in PTMs of MT lead to pathology of the auditory pathway? For this purpose, the influence of different glutamylation of MT on the auditory pathway will be investigated using tubulin tyrosine ligases and carboxypeptidases knockout animals. 2) Is a correct MT dynamic important for the function of supporting cells? Therefore, the function of Stathmin1, a protein that regulates MT dynamics and is highly selectively expressed in Deiters´ cells, will be evaluated by crossing a Deiters´ cell specific Cre mouse (Fgfr3-iCre) with a Stathmin1 loxP mouse. Electrophysiological measurements and histological preparations will be used, which will be evaluated by light, fluorescence and electron microscopy. In summary, the studies will provide further insights into MT dynamics on the development and integrity of the organ of Corti.

• DFG Programme: Research Grants