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Aneuploidy in Human Oocytes and Preimplantation Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Microtubules are composed of alpha and beta tubulin subunits. Recently, mutations in TUBB8, the major β-tubulin expressed only in oocytes and preimplantation embryos, were shown to be associated with maturation arrest (104) as well as defective divisions in both oocytes and embryos (104–106). TUBB8 is particularly interesting because it evolved in the primate clade and could thus contribute to the substantial differences in spindle dynamics in mouse and human oocytes.
Genetic Analysis of Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Although several variants of both alpha- and beta-tubulins have been identified in somatic cells, mature sperm of the fruit fly Drosophila contain only one form of beta-tubulin, called beta2-tubulin. The gene for this protein, B2t, is expressed only in the testis.1 Analysis of B2t mutations which produce no stable product has shown that the same isoform of tubulin is used for many functionally different types of microtubules. Males carrying this class of mutations are defective in axonemal formation, meiosis, and nuclear shaping. Cytoplasmic microtubules, centrioles, and the spindles of mitotic divisions preceding meiosis, on the other hand, are unaffected by these mutations.2 Thus, beta2-tubulin is used in all of the specialized arrays of microtubules necessary for spermiogenesis. This implies that assembly of beta-tubulin into axonemal microtubules must be dictated by other components, such as alpha-tubulin variants, posttranslational modification of tubulin subunits, or microtubule-associated proteins (MAPS).
The Aging of the Neuronal Cytoskeleton
Published in Alvaro Macieira-Coelho, Molecular Basis of Aging, 2017
P. Klosen, Ph. van den Bosch de Aguilar
Microtubules, the third cytoskeletal component, are hollow tubes of 25 nm diameter formed by protofilaments composed of alpha and beta tubulin heterodimers. Like actin, the tubulins are highly conserved proteins and microtubule functionality is thus modulated by a family of associated proteins to adapt the microtubule cytoskeleton to the needs of different cell types. These proteins are called MAPs, for microtubule-associated proteins.9–11 The diversity of both tubulin isoforms and MAPs is highest in the brain, illustrating the importance of microtubules in neurons. Three main functions are executed by MAPs: microtubule stabilization, microtubule cross-linking, and organelle transport along microtubules. Like actin filaments, microtubules are mostly unstable filaments whose polymerization is often characterized as a dynamic equilibrium controlled by the concentration of tubulin monomers, GTP and calcium, as well as MAPs like the tau protein. The recently discovered gamma-tubulin acts as microtubule nucleating protein.12,13 This protein, whose concentration in individual cells is extremely low, is located in the microtubule organizing center (MTOC). The MTOC is an area normally located close to the nucleus from which microtubules irradiate throughout the cytoplasm. It is noteworthy that intermediate filaments also seem to irradiate from this area. However, the interaction of intermediate filaments with the MTOC has not been studied so far.
Investigation of apoptotic and antiproliferative effects of Turkish natural tetraploids Trifolium pratense L. extract on C6 glioblastoma cells via light and electron microscopy
Published in Ultrastructural Pathology, 2023
Gamze Tanrıverdi, Aynur Abdulova, Hatice Çölgeçen, Havva Atar, Belisa Kaleci, Tuğba Ekiz-Yılmaz
Beta-tubulin is a structural monomer found in microtubules in the C6 glioblastoma cells and is responsible for maintaining the elongated shape of the cell. In order to understand the structural effects of Trifolium pratense L. on these cells, all of the groups were stained by β-tubulin, immunocytochemically. Diffuse localization of the β-tubulin was clearly observed in the control group while it was forming clusters in the groups with increasing doses. This cluster’s forms were prominent especially at 25 µg/mL and 12.5 µg/mL applied doses which belonged to the 24 h and 48 h, respectively. And also, morphological changes and deformation in C6 glioblastoma cells, deterioration both in tubule structure and intercellular connections were detected as a result of the increasing doses of Trifolium pratense L. (Figure 3).
Cabazitaxel-loaded poly(alkyl cyanoacrylate) nanoparticles: toxicity and changes in the proteome of breast, colon and prostate cancer cells
Published in Nanotoxicology, 2021
Anders Øverbye, Maria Lyngaas Torgersen, Tonje Sønstevold, Tore Geir Iversen, Ýrr Mørch, Tore Skotland, Kirsten Sandvig
Proteomic analyses of HCT116 cells treated with increasing concentrations (3 and 10 nM) of CBZ (Scenario 2 in Table 2) gave up-regulation of proteins (Figure 6(A & B), Supplementary Table 1) involved in ketone catabolism, glycolysis (labeled red in the figure) and cytoskeleton organization (labeled blue in the figure), i.e. in processes involved in initiating decreased cellular viability. A majority of the enriched proteins were involved in ribonuclear assembly (labeled green). Noteworthy is also the increase in isoforms of beta-tubulin (TUBB2a, TUBB4b, TUBB3a and TUBB8), which indicates that newly synthesized tubulin is formed to address the increase in microtubule stabilization caused by the highest dose of CBZ. On the other side, higher concentrations of CBZ resulted in reduced levels of proteins (Figure 6(C & D), Supplementary Table 1) known to be involved in cell division and translation (labeled in green and blue) and in general an apparent larger transcriptional regulation. In particular, the absence of KRAS (gray in Figure 6(C); or its undistinguishable homologues NRAS/HRAS) after increased CBZ is interesting as RAS is an important oncogene and driver of the Raf/ERK-cascade (Santos and Crespo 2018). A subset of the depleted proteins has a role in ER/ribosome functions, indicative of general reduction in protein production (labeled red and orange).
Actinic keratosis: where do we stand and where is the future going to take us?
Published in Expert Opinion on Emerging Drugs, 2020
Philipp Cramer, Eggert Stockfleth
Nanology is developing a nanoparticle formulation of Paclitaxel in ointment. It is targeting a variety of cancers, AK, psoriasis as well as cervical intraepithelial neoplasia [68]. On a biological level, it targets tubulin beta class I and acts as a beta tubulin antagonist and microtubule stimulant [68]. By this mechanism, Paclitaxel inhibits cell division and thereby targets fast proliferating cells [70,71]. Paclitaxel is patented under US9814685 which is set to expire in 2036 [68]. Preclinical studies, including histological analysis, showed that topical treatment results in a significant decrease in tumor cells and tumor regression whilst showing minimal dermal irritation and negligible systemic absorption [72,73]. In 2017, a phase II randomized, double blind clinical trial in 32 patients with AK was completed [74]. This phase II trial was designed to test four strengths of the product for safety, tolerability, and preliminary efficacy with an application period of 28 days. Results show evidence of a significant reduction in size as well as count correlating with a dose-dependent responds and minimal dermal irritation [75].