Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities.
Autor: | Pfaltzgraff ER; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232., Roth GM; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232., Miller PM; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232., Gintzig AG; Division of Hematology-Oncology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232., Ohi R; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232 ryoma.ohi@vanderbilt.edu david.bader@vanderbilt.edu., Bader DM; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232 ryoma.ohi@vanderbilt.edu david.bader@vanderbilt.edu. |
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Jazyk: | angličtina |
Zdroj: | Molecular biology of the cell [Mol Biol Cell] 2016 Jul 01; Vol. 27 (13), pp. 1990-9. Date of Electronic Publication: 2016 May 04. |
DOI: | 10.1091/mbc.E15-12-0848 |
Abstrakt: | Microtubule (MT)-binding centromere protein F (CENP-F) was previously shown to play a role exclusively in chromosome segregation during cellular division. Many cell models of CENP-F depletion show a lag in the cell cycle and aneuploidy. Here, using our novel genetic deletion model, we show that CENP-F also regulates a broader range of cellular functions outside of cell division. We characterized CENP-F(+/+) and CENP-F(-/-) mouse embryonic fibroblasts (MEFs) and found drastic differences in multiple cellular functions during interphase, including cell migration, focal adhesion dynamics, and primary cilia formation. We discovered that CENP-F(-/-) MEFs have severely diminished MT dynamics, which underlies the phenotypes we describe. These data, combined with recent biochemical research demonstrating the strong binding of CENP-F to the MT network, support the conclusion that CENP-F is a powerful regulator of MT dynamics during interphase and affects heterogeneous cell functions. (© 2016 Pfaltzgraff et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).) |
Databáze: | MEDLINE |
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