Journal article
Differential expression of human gamma-tubulin isotypes during neuronal development and oxidative stress points to a gamma-tubulin-2 prosurvival function
The FASEB journal, v 31(5), pp 1828-1846
01 May 2017
PMID: 28119396
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
gamma-Tubulins are highly conserved members of the tubulin superfamily essential for microtubule nucleation. Humans possess 2 gamma-tubulin genes. It is thought that gamma-tubulin-1 represents aubiquitous isotype, whereas gamma-tubulin-2 is found predominantly in the brain, where it may be endowed with divergent functions beyond microtubule nucleation. The molecular basis of the purported functional differences between gamma-tubulins is unknown. We report discrimination of human gamma-tubulins according to their electrophoretic and immunochemical properties. In vitro mutagenesis revealed that the differences in electrophoretic mobility originate in the C-terminal regions of the gamma-tubulins. Using epitope mapping, we discovered mouse monoclonal antibodies that can discriminate between human gamma-tubulin isotypes. Real time quantitative RT-PCR and 2-dimensional-PAGE showed that gamma-tubulin-1 is the dominant isotype in fetal neurons. Although gamma-tubulin-2 accumulates in the adult brain, gamma-tubulin-1 remains the major isotype in various brain regions. Localization of gamma-tubulin-1 in mature neurons was confirmed by immunohistochemistry and immunofluorescence microscopy on clinical samples and tissue microarrays. Differentiation of SH-SY5Y human neuroblastoma cells by all-trans retinoic acid, or oxidative stress induced by mitochondrial inhibitors, resulted in upregulation of gamma-tubulin-2, whereas the expression of gamma-tubulin-1 was unchanged. Fractionation experiments and immunoelectron microscopy revealed an association of gamma-tubulins with mitochondrial membranes. These data indicate that in the face of predominant nu-tubulin-1 expression, the accumulation of gamma-tubulin-2 in mature neurons and neuroblastoma cells during oxidative stress may denote a prosurvival role of gamma-tubulin-2 in neurons.-Draberova, E., Sulimenko, V., Vinopal, S., Sulimenko, T., Sladkova, V., D'Agostino, L., Sobol, M., Hozak, P., Kren, L., Katsetos, C. D., Draber, P. Differential expression of human gamma-tubulin isotypes during neuronal development and oxidative stress points to gamma-tubulin-2 prosurvival function.
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Details
- Title
- Differential expression of human gamma-tubulin isotypes during neuronal development and oxidative stress points to a gamma-tubulin-2 prosurvival function
- Creators
- Eduarda Draberova - Cytoskeleton (United States)Vadym Sulimenko - Cytoskeleton (United States)Stanislav Vinopal - Cytoskeleton (United States)Tetyana Sulimenko - Cytoskeleton (United States)Vladimira Sladkova - Cytoskeleton (United States)Luca D'Agostino - Drexel UniversityMargaryta Sobol - Academy of Sciences of the Czech RepublicPavel Hozak - Academy of Sciences of the Czech RepublicLeos Kren - §Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, St. Christopher’s Hospital for Children and Hahnemann University Hospital, Philadelphia, Pennsylvania, USA; andChristos D. Katsetos - Drexel UniversityPavel Draber - Cytoskeleton (United States)
- Publication Details
- The FASEB journal, v 31(5), pp 1828-1846
- Publisher
- Wiley
- Number of pages
- 19
- Grant note
- 302/12/1673; 15-22194S; 16-25159S / Grant Agency of the Czech Republic RVO 68378050 / Institutional Research Support Program TE01020118 / Technological Grant Agency of the Czech Republic NT14467 / Ministry of Health of the Czech Republic; Ministry of Health, Czech Republic LH 12050; LM 2015062 / Ministry of Education, Youth, and Sports of the Czech Republic; Ministry of Education, Youth & Sports - Czech Republic M200521203PIP / Academy of Sciences of the Czech Republic; Czech Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000399195500007
- Scopus ID
- 2-s2.0-85019501996
- Other Identifier
- 991019353724304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology