Abstract
The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing.
Highlights
The organ of Corti, located in the cochlea, is the receptor organ for hearing
These findings provide insight into the complex intracellular changes in MT distribution and function occurring during early postnatal development
The distribution of tubulin-binding cofactors (TBC) proteins and Posttranslational modifications (PTMs) of tubulin are described for the first time in the postnatal developing murine cochlea
Summary
The organ of Corti, located in the cochlea, is the receptor organ for hearing. Auditory signals are converted into action potentials that are transmitted to the auditory brainstem for further processing. It was found that a missense mutation of the TBCE gene leads to progressive motor neuropathy and hearing loss in mice (Bommel et al 2002; Volkenstein et al 2009) The latter is caused by selective apoptosis of the outer hair cells of the organ of Corti and a disturbed MT distribution of the auditory nerve fibres (Rak et al 2013). While all three isotopes are expressed in all cell types at P0, cell-type-specific reductions occur which lead to different isotype combinations in each cell type These findings provide insight into the complex intracellular changes in MT distribution and function occurring during early postnatal development. The results of these investigations will lead to a deeper understanding of the specific development of cochlear cells and possibly help to clarify why different cells show their distinct cellular morphology, which may be linked to altered stability due to differences in the MT distribution
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