China
Africa
Explore chapters and articles related to this topic
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Microtubules have an external diameter of 25 nm and a length varying from 250 nm to 25 µm. Their dynamic properties are based on their inherent structure and polarity, which is dependent upon the tubulin isoforms from which they derive. At present, six isoforms of tubulin are known within eukaryotic cells: alpha-(α), beta-(β), gamma-(γ), delta-(δ), epsilon-(ε), and zeta-(ζ) tubulins), with each isoform containing a number of subtypes. For example, the beta-(β) subtypes include TUBB, TUBB1, TUBB2A, TUBB2B, TUBB2C, TUBB3, TUBB4, TUBB4Q, TUBB6, and TUBB8. The alpha-(α) and beta-(β) isoforms form the structure of the polymeric form of tubulin which constitutes the microtubules, and γ-tubulin functions as a template for the correct assembly of microtubules. These isoforms, which each have a molecular weight of approximately 50 kDa, can be further modified by various post-translational modifications, including tyrosination and de-tyrosination, acetylation, polyglutamylation, polyglycylation, phosphorylation, and palmitoylation. Except for tubulin tyrosine ligase (the enzyme that adds a tyrosine to nonassembled α-tubulin), most of the modifying enzymes act preferentially on tubulin subunits that are already incorporated into microtubules. Post-translational modifications of tubulin subunits appear to mark sub-populations of microtubules, selectively affecting their functions. Although they are not directly involved in determining the dynamic properties of microtubules, modifications such as sequential tyrosination/de-tyrosination/acetylation correlate well with the half-life and spatial distribution of microtubules.
The role of microtubules in the regulation of epithelial junctions
Published in Tissue Barriers, 2018
Ekaterina Vasileva, Sandra Citi
Among different types of cytoskeletal polymers, microtubules (MTs), along with actin filaments, are the most evolutionarily conserved, since they are present in all eukaryotes, where they promote the generation of mechanical force and movement through kinesin and dynein (for MTs), and myosin (for actin filaments) motors, respectively. Although proteins similar to tubulin and actin are also found in prokaryotes, the associated protein motors appear to be missing.1 MTs are hollow cylindrical polymers of heterodimeric subunits made of α- and β-tubulin, and are typically made up of 13 parallel protofilaments.2 They are polarized, with plus ends, which are highly dynamic, undergoing either rapid polymerization or rapid depolymerization (catastrophe), and minus ends, which are typically either stabilized or acting as sites of depolymerization.3 Polymerizing MTs are nucleated and stabilized at their minus ends by the γ-tubulin ring complex (γ-TuRC). The γ-TuRC is the main structural unit of microtubule organizing centers (MTOCs), which are found both at centrosomes, and at non-centrosomal sites, such as the Golgi apparatus.4 Tubulins are targets for numerous types of post-translational modifications (PTMs) affecting their C-terminal sequences, including de-tyrosination, Δ2-tubulin generation, polyglutamylation, polyglycylation, and acetylation.5 The functional significance and mechanisms of tubulin PTMs have been investigated in neuronal cells, where PTMs regulate MTs organization and interactions with motors, but their role in epithelial cells is less clear.