The microtubule skeleton and the evolution of neuronal complexity in vertebrates

Abstract

The evolution of a highly developed nervous system is mirrored by the ability of individual neurons to develop increased morphological complexity. As microtubules (MTs) are crucially involved in neuronal development, we tested the hypothesis that the evolution of complexity is driven by an increasing capacity of the MT system for regulated molecular interactions as it may be implemented by a higher number of molecular players and a greater ability of the individual molecules to interact. We performed bioinformatics analysis on different classes of components of the vertebrate neuronal MT cytoskeleton. We show that the number of orthologs of tubulin structure proteins, MT-binding proteins and tubulin-sequestering proteins expanded during vertebrate evolution. We observed that protein diversity of MT-binding and tubulin-sequestering proteins increased by alternative splicing. In addition, we found that regions of the MT-binding protein tau and MAP6 displayed a clear increase in disorder extent during evolution. The data provide evidence that vertebrate evolution is paralleled by gene expansions, changes in alternative splicing and evolution of coding sequences of components of the MT system. The results suggest that in particular evolutionary changes in tubulin-structure proteins, MT-binding proteins and tubulin-sequestering proteins were prominent drivers for the development of increased neuronal complexity.

The Evolution of Tau Phosphorylation and Interactions

“…Previously, we reported a tendency of increased disorder of tau protein structure during evolution, a feature, which tau shared with MAP6 protein, which is involved in stabilization of axonal microtubules (Tortosa et al, 2017). In contrast, we did not observe a similar increase in disorder in the structure of the somatodendritic MAP2 protein (Trushina et al, 2019). Since IDRs provide a larger interaction surface area and are known to be hubs for cellular interactions, different tau regions may differ in their extent of disorder.…”

“…Thus, an increase in IDRs during evolution may provide a mechanism for increased binding promiscuity and improved ability to adapt to changes in the environment. This suggests that in particular tau’s potential functions with respect to membrane organization and regulation of apoptotic processes, which are both predominantly mediated via the NTR, were beneficial for the development of a complex nervous system, which is paralleled by an increased ability of the microtubule system for regulated interactions (Trushina et al, 2019). The involvement of IDPs such as tau in neurodegenerative diseases of mammals could then be interpreted in the context of the “antagonistic pleiotropy hypothesis,” as it was first proposed by Williams (1957).…”

“…These regions may also have contributed to tau’s malfunction during the development of tauopathies, which occur in higher vertebrates. In fact, the NTR and PRR contain IDRs, which may play diverse roles in the modulation and control of the functions of many different binding partners (Uversky, 2015; Trushina et al, 2019). Alternatively spliced exons of tau CNS isoforms code for regions that are located in the NTR (exon 2 and 3) and in the MBR (exon 10); exon 10 codes for an additional microtubule-interacting site (Figure 4B).…”

“…We have previously provided evidence that evolutionary changes in tubulin-structure proteins, MT-binding proteins and tubulin-sequestering proteins are prominent drivers for the development of increased neuronal complexity (Trushina et al, 2019). We also provided evidence that tau displays an increase in disorder extent during evolution.…”

New C-Terminal Conserved Regions of Tafazzin, a Catalyst of Cardiolipin Remodeling

“…The identified regions cannot be aligned to domains involved in enzyme activity, which gives no grounds to assume their participation in protein attachment to the mitochondrial inner membrane or being a part of the catalytic center. Similarly, disordered regions have been found at the N termini of microtubule-binding and tubulin-sequestering proteins [24].…”