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.

Department of Oncology University of Alberta Cross Cancer Institute 11560 University Avenue Edmonton AB T6G 1Z2 Canada

DIMEAS Politecnico di Torino Corso Duca degli Abruzzi 24 10129 Torino Italy

Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 Prague 142 20 Czech Republic

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Yeh I.T., Luduena R.F. The betaII isotype of tubulin is present in the cell nuclei of a variety of cancers. Cell Motil. Cytoskelet. 2004;57:96–106. doi: 10.1002/cm.10157. PubMed DOI

Walss-Bass C., Kreisberg J.I., Luduena R.F. Effect of the antitumor drug vinblastine on nuclear betaII-tubulin in cultured rat kidney mesangial cells. Investig. New Drugs. 2003;21:15–20. doi: 10.1023/A:1022947706151. PubMed DOI

Xu K., Luduena R.F. Characterization of nuclear betaII-tubulin in tumor cells: A possible novel target for taxol. Cell Motil. Cytoskelet. 2002;53:39–52. doi: 10.1002/cm.10060. PubMed DOI

Puurand M., Tepp K., Timohhina N., Aid J., Shevchuk I., Chekulayev V., Kaambre T. Tubulin betaII and betaIII Isoforms as the Regulators of VDAC Channel Permeability in Health and Disease. Cells. 2019;8:239. doi: 10.3390/cells8030239. PubMed DOI PMC

Majcher U., Klejborowska G., Moshari M., Maj E., Wietrzyk J., Bartl F., Tuszynski J.A., Huczynski A. Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives. Cells. 2018;7:192. doi: 10.3390/cells7110192. PubMed DOI PMC

Keays D.A., Tian G., Poirier K., Huang G.J., Siebold C., Cleak J., Oliver P.L., Fray M., Harvey R.J., Molnar Z., et al. Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell. 2007;128:45–57. doi: 10.1016/j.cell.2006.12.017. PubMed DOI PMC

Yuba-Kubo A., Kubo A., Hata M., Tsukita S. Gene knockout analysis of two gamma-tubulin isoforms in mice. Dev. Biol. 2005;282:361–373. doi: 10.1016/j.ydbio.2005.03.031. PubMed DOI

Mencarelli A., Prontera P., Stangoni G., Mencaroni E., Principi N., Esposito S. Epileptogenic Brain Malformations and Mutations in Tubulin Genes: A Case Report and Review of the Literature. Int. J. Mol. Sci. 2017;18:2273. doi: 10.3390/ijms18112273. PubMed DOI PMC

Wagstaff J., Lowe J. Prokaryotic cytoskeletons: Protein filaments organizing small cells. Nat. Rev. Microbiol. 2018;16:187–201. doi: 10.1038/nrmicro.2017.153. PubMed DOI

Chumova J., Trogelova L., Kourova H., Volc J., Sulimenko V., Halada P., Kucera O., Benada O., Kucharova A., Klebanovych A., et al. gamma-Tubulin has a conserved intrinsic property of self-polymerization into double stranded filaments and fibrillar networks. Biochim. Biophys. Acta. Mol. Cell Res. 2018;1865:734–748. doi: 10.1016/j.bbamcr.2018.02.009. PubMed DOI

Rossello C.A., Lindstrom L., Glindre J., Eklund G., Alvarado-Kristensson M. Gamma-tubulin coordinates nuclear envelope assembly around chromatin. Heliyon. 2016;2:e00166. doi: 10.1016/j.heliyon.2016.e00166. PubMed DOI PMC

Lebok P., Ozturk M., Heilenkotter U., Jaenicke F., Muller V., Paluchowski P., Geist S., Wilke C., Burandt E., Lebeau A., et al. High levels of class III beta-tubulin expression are associated with aggressive tumor features in breast cancer. Oncol. Lett. 2016;11:1987–1994. doi: 10.3892/ol.2016.4206. PubMed DOI PMC

Narvi E., Jaakkola K., Winsel S., Oetken-Lindholm C., Halonen P., Kallio L., Kallio M.J. Altered TUBB3 expression contributes to the epothilone response of mitotic cells. Br. J. Cancer. 2013;108:82–90. doi: 10.1038/bjc.2012.553. PubMed DOI PMC

Ruksha K., Mezheyeuski A., Nerovnya A., Bich T., Tur G., Gorgun J., Luduena R., Portyanko A. Over-Expression of betaII-Tubulin and Especially Its Localization in Cell Nuclei Correlates with Poorer Outcomes in Colorectal Cancer. Cells. 2019;8:25. doi: 10.3390/cells8010025. PubMed DOI PMC

Katsetos C.D., Reddy G., Draberova E., Smejkalova B., Del Valle L., Ashraf Q., Tadevosyan A., Yelin K., Maraziotis T., Mishra O.P., et al. Altered cellular distribution and subcellular sorting of gamma-tubulin in diffuse astrocytic gliomas and human glioblastoma cell lines. J. Neuropathol. Exp. Neurol. 2006;65:465–477. doi: 10.1097/01.jnen.0000229235.20995.6e. PubMed DOI

Horejsi B., Vinopal S., Sladkova V., Draberova E., Sulimenko V., Sulimenko T., Vosecka V., Philimonenko A., Hozak P., Katsetos C.D., et al. Nuclear gamma-tubulin associates with nucleoli and interacts with tumor suppressor protein C53. J. Cell Physiol. 2012;227:367–382. doi: 10.1002/jcp.22772. PubMed DOI

Chumova J., Kourova H., Trogelova L., Halada P., Binarova P. Microtubular and Nuclear Functions of gamma-Tubulin: Are They LINCed? Cells. 2019;8:259. doi: 10.3390/cells8030259. PubMed DOI PMC

Barbuti A.M., Chen Z.S. Paclitaxel Through the Ages of Anticancer Therapy: Exploring Its Role in Chemoresistance and Radiation Therapy. Cancers. 2015;7:2360–2371. doi: 10.3390/cancers7040897. PubMed DOI PMC

Savry A., Carre M., Berges R., Rovini A., Pobel I., Chacon C., Braguer D., Bourgarel-Rey V. Bcl-2-enhanced efficacy of microtubule-targeting chemotherapy through Bim overexpression: Implications for cancer treatment. Neoplasia. 2013;15:49–60. doi: 10.1593/neo.121074. PubMed DOI PMC

Whitaker R.H., Placzek W.J. Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents. Cells. 2019;8:346. doi: 10.3390/cells8040346. PubMed DOI PMC

Anmann T., Varikmaa M., Timohhina N., Tepp K., Shevchuk I., Chekulayev V., Saks V., Kaambre T. Formation of highly organized intracellular structure and energy metabolism in cardiac muscle cells during postnatal development of rat heart. Biochim. Biophys. Acta. 2014;1837:1350–1361. doi: 10.1016/j.bbabio.2014.03.015. PubMed DOI

Romaniello R., Zucca C., Arrigoni F., Bonanni P., Panzeri E., Bassi M.T., Borgatti R. Epilepsy in Tubulinopathy: Personal Series and Literature Review. Cells. 2019;8:669. doi: 10.3390/cells8070669. PubMed DOI PMC

Ivanova E.L., Gilet J.G., Sulimenko V., Duchon A., Rudolf G., Runge K., Collins S.C., Asselin L., Broix L., Drouot N., et al. TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis. Nat. Commun. 2019;10:2129. doi: 10.1038/s41467-019-10081-8. PubMed DOI PMC

Smith A.J., Pfeiffer J.R., Zhang J., Martinez A.M., Griffiths G.M., Wilson B.S. Microtubule-dependent transport of secretory vesicles in RBL-2H3 cells. Traffic. 2003;4:302–312. doi: 10.1034/j.1600-0854.2003.00084.x. PubMed DOI

Hajkova Z., Bugajev V., Draberova E., Vinopal S., Draberova L., Janacek J., Draber P., Draber P. STIM1-directed reorganization of microtubules in activated mast cells. J. Immunol. 2011;186:913–923. doi: 10.4049/jimmunol.1002074. PubMed DOI

Nishida K., Yamasaki S., Ito Y., Kabu K., Hattori K., Tezuka T., Nishizumi H., Kitamura D., Goitsuka R., Geha R.S., et al. Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane. J. Cell Biol. 2005;170:115–126. doi: 10.1083/jcb.200501111. PubMed DOI PMC

Sulimenko V., Draberova E., Sulimenko T., Macurek L., Richterova V., Draber P., Draber P. Regulation of microtubule formation in activated mast cells by complexes of gamma-tubulin with Fyn and Syk kinases. J. Immunol. 2006;176:7243–7253. doi: 10.4049/jimmunol.176.12.7243. PubMed DOI

Draberova L., Draberova E., Surviladze Z., Draber P., Draber P. Protein tyrosine kinase p53/p56(lyn) forms complexes with gamma-tubulin in rat basophilic leukemia cells. Int. Immunol. 1999;11:1829–1839. doi: 10.1093/intimm/11.11.1829. PubMed DOI

Sulimenko V., Hajkova Z., Cernohorska M., Sulimenko T., Sladkova V., Draberova L., Vinopal S., Draberova E., Draber P. Microtubule nucleation in mouse bone marrow-derived mast cells is regulated by the concerted action of GIT1/betaPIX proteins and calcium. J. Immunol. 2015;194:4099–4111. doi: 10.4049/jimmunol.1402459. PubMed DOI

Klebanovych A., Sladkova V., Sulimenko T., Vosecka V., Capek M., Draberova E., Draber P., Sulimenko V. Regulation of Microtubule Nucleation in Mouse Bone Marrow-Derived Mast Cells by Protein Tyrosine Phosphatase SHP-1. Cells. 2019;8:345. doi: 10.3390/cells8040345. PubMed DOI PMC

Oakley B.R., Paolillo V., Zheng Y. gamma-Tubulin complexes in microtubule nucleation and beyond. Mol. Biol. Cell. 2015;26:2957–2962. doi: 10.1091/mbc.E14-11-1514. PubMed DOI PMC

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