Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice

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. Electronic supplementary material The online version of this article (10.1007/s00418-020-01905-6) contains supplementary material, which is available to authorized users.

Effects of acute exposure to Al2O3-NPs (α and γ) and white noise and their combination on Cochlea structure and function in Wistar Rat

“…Myosin-VIIa is a motor protein that plays a crucial role in forming and maintaining stereocilia in hair cells and the vestibular system (Sirko &Kozlov 2022). ß-Tubulin is located in SGCs and dendrites (Juergens et al 2020).…”

Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti

“…This TULP3 staining pattern became successively more pronounced during the postnatal development and additionally well-defined filamentous TULP3-positive structures emerged in the OHC region at this age (Figure 5). Supporting cells including pillar cells and Deiters' cells (DCs') provide structural support to the auditory epithelium by virtue of highly specialized microtubule-rich structures (Liu et al, 2018;Juergens et al, 2020;Chen et al, 2021). Given the known association of TULP proteins with tubulin-based ciliary structures, we wondered whether the observed TULP3-positive non-ciliary structures might correspond to microtubule bundles in the basolateral domain of non-sensory supporting cells.…”

From Posttranslational Modifications to Disease Phenotype: A Substrate Selection Hypothesis in Neurodegenerative Diseases

“…The substrate selection hypothesis explains how PTMs define the preferences of differentially modified protein isoforms to be recruited by structurally heterogeneous protofibrils. Assuming that PTMs metabolism is regulated in a cell type-, brain region- and age-specific manner [ 73 , 74 , 75 ], do PTMs play a role in defining strain identity and heterogeneity of self-replicating states of sporadic origin?…”

“…As much as metabolism of PTMs is specified by a brain region, cell type and age [ 73 , 74 , 75 ], constrains imposed by PTMs on self-replicating states are also expected to be cell-, region- and age-specific. One might suggest that the cell type and brain region, from which self-propagating states originate, along with an age of an individual, are important parameters dictating an identity of strains of sporadic origin.…”