Structure and Function of Cartilage
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi in Articular Cartilage, 2017
Microtubules differ from actin and intermediate filaments in terms of both size and filament construction. Tubulin is a heterodimer composed of α/β monomers 55 kDa in size. It self-assembles into hollow 23 nm diameter “tubes” forming the microtubules, with an internal lumen diameter on the order of 15 nm. GTP binding is required for this assembly, and tubulin has GTPase activity, with GTP hydrolysis driving microtubule assembly. Microtubules also differ in their role in resisting force, acting to resist compression more than tension. The cilia and flagella (including the primary cilium) are composed of a microtubule arrangement described as 9 + 2, featuring an outer circle of nine microtubule doublets interconnected with dynein and with an inner arrangement of two microtubules. In addition to resisting compressive force, microtubules are also critically important in intracellular transport of organelles or vesicles through the actions of the dynein and kinesin motor proteins. The role of microtubules in intracellular transport is elegantly demonstrated in the assembly of the mitotic spindle, a structure that results in the intracellular movement and segregation of the replicated DNA into two daughter cells during mitosis.
Immunology of lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
The humoral response to autoantigens has included identification of col(V) and K-a1 tubulin (Ka1T) antibodies as a pathophysiologic component of BOS in preclinical models (Figure 2.2).74,75 K-a1 tubulin is a protein constituent of microtubules that provides cytoskeletal structure as a part of normal cellular function.76 Ka1T exposure may result from chronic injury to the airway epithelium, and col(V) exposure may result from similar inciting events. Additionally, cell surface expression can occur under certain circumstances. Anti-Ka1T antibody binding to airway epithelial cells results in transcription of the factors involved in fibroproliferation, a hallmark of OB.74 Clinically, the presence of anti-col(V) and anti-Ka1T after transplantation has been strongly associated with BOS.77 Furthermore, anti-col(V) and anti- Ka1T have been found in a subset of patients before transplantation, which is probably a result of their end-stage pulmonary disease—which increases the risk for BOS as well.47,78
Genetic Analysis of Sperm Motility
Claude Gagnon in 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).
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).
Cerebrospinal fluid proteomics reveal potential protein targets of JiaWeiSiNiSan in preventing chronic psychological stress damage
Published in Pharmaceutical Biology, 2021
Han-Zhang Wang, Wu-Long Luo, Ning-Xi Zeng, Hui-Zhen Li, Ling Li, Can Yan, Li-Li Wu
Highly conserved tubulin-β and tubulin-α assemble into dynamic microtubules that perform a variety of important cellular functions such as structural support, transport and stress generation in cell division. As cellular partners of HtrA3, tubulin-β, actin and TCP1 protein may influence cytoskeletal dynamics. Tubulin plays an important role in the nervous system. Mutations in tubulin-αβ dimers and tubulin-γ can cause brain malformations and impair cognitive function (Keays et al. 2007). In this study, levels of tubulin-β in cerebrospinal fluid of CUMS rats were increased, while those in the CUMS + JWSNS group were down-regulated. It was suggested that the increase of tubulin-β in CSF of CUMS rats may be related to the death of neurons and gliocyte, while the compensatory increase of cytoskeleton may be related, which was not observed in CUMS + JWSNS group.
Discovery of dual tubulin-NEDDylation inhibitors with antiproliferative activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Microtubules as dynamic protein polymers of α- and β-tubulin play essential roles in a range of cellular processes, such as intracellular transport, cell division, cell growth, cell shape maintenance, and cell motility1. Recently, microtubule-targeting agents interacted with tubulin have been widely developed for cancer therapy2. N-substituted 3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid derivative 1 (Figure 1) inhibited tubulin polymerisation and exhibited the potent antiproliferative activity3. Tubulin polymerisation inhibitor 2 could induce intracellular reactive oxygen species (ROS) production and mitochondrial depolarization4. Compound 3 induced the G2/M phase arrest and cell apoptosis against MGC803 cells by targeting tubulin5. Tubulin polymerisation inhibitor 4 could interrupt the formation of microtubule network by inhibiting the tubulin polymerisation with an IC50 value of 4.96 μM6. Thus, tubulin has become an important target for the development of anticancer agents7.
Related Knowledge Centers
- Cytoskeleton
- DNA
- Eukaryote
- Globular Protein
- Microtubule
- Molecular Biology
- Cancer
- Mitosis
- Protein Superfamily
- Discovery & Development of Tubulin Inhibitors