Tubulin: Structure, Functions and Roles in Disease

Abstract

Highly conserved α- and β-tubulin heterodimers assemble into dynamic microtubules and perform multiple important cellular functions such as structural support, pathway for transport and force generation in cell division. Tubulin exists in different forms of isotypes expressed by specific genes with spatially- and temporally-regulated expression levels. Some tubulin isotypes are differentially expressed in normal and neoplastic cells, providing a basis for cancer chemotherapy drug development. Moreover, specific tubulin isotypes are overexpressed and localized in the nuclei of cancer cells and/or show bioenergetic functions through the regulation of the permeability of mitochondrial ion channels. It has also become clear that tubulin isotypes are involved in multiple cellular functions without being incorporated into microtubule structures. Understanding the mutations of tubulin isotypes specifically expressed in tumors and their post-translational modifications might help to identify precise molecular targets for the design of novel anti-microtubular drugs. Knowledge of tubulin mutations present in tubulinopathies brings into focus cellular functions of tubulin in brain pathologies such as Alzheimer’s disease. Uncovering signaling pathways which affect tubulin functions during antigen-mediated activation of mast cells presents a major challenge in developing new strategies for the treatment of inflammatory and allergic diseases. γ-tubulin, a conserved member of the eukaryotic tubulin superfamily specialized for microtubule nucleation is a target of cell cycle and stress signaling. Besides its microtubule nucleation role, γ-tubulin functions in nuclear and cell cycle related processes. This special issue “Tubulin: Structure, Functions and Roles in Disease” contains eight articles, five of which are original research papers and three are review papers that cover diverse areas of tubulin biology and functions under normal and pathological conditions.

Altered cytoskeletal arrangement in induced pluripotent stem cells and motor neurons from patients with riboflavin transporter deficiency

“…As patients' iPSCs fail to form well-defined round-shaped colonies, we decided to further characterize their cytoskeletal architecture. We focused on MTs, as alterations to these structures or to MT-associated or MT-regulating proteins may impair neuronal morphology and function ( Gonçalves et al, 2018 ; Binarová and Tuszynski, 2019 ). To this aim, we investigated the distribution and levels of α-TUB and β-TUB, which are major components of microtubules ( Fig.…”

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

“…Microtubules are dynamic cellular structures responsible for various processes in the eukaryotic cell. They play an important role in motility, mitotic apparatus formation and cell division, angiogenesis, metastasis, maintenance of cell shape, and transport of organelles and other cell components [ 178 ]. The major component of microtubules is the heterodimeric globular protein tubulin.…”

Oscillating field stimulation promotes recovery from spinal cord injury in rats by regulating the differentiation of endogenous neural stem cells

“…The BBB scores revealed substantially faster and improved locomotor improvement in the SCI + OFS group compared with the SCI group with no apparent adverse effects on survival of rats, indicating that OFS is a feasible strategy for the treatment of SCI. β-tubulin is one of the main components of the cytoskeleton and the class III isoform is expressed exclusively in neurons, where it contributes to morphological development and axon orientation (30). NSCs promote SC repair by enhancing neuronal viability, reducing neuroinflammation and replenishing cells lost to apoptosis (31).…”