Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities
| Autor: | Elise R. Pfaltzgraff, Anneelizabeth G. Gintzig, Gretchen M. Roth, Paul M. Miller, David M. Bader, Ryoma Ohi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cell division Chromosomal Proteins Non-Histone Centromere Mitosis macromolecular substances Biology Microtubules 03 medical and health sciences Mice Microtubule Chromosome Segregation Animals skin and connective tissue diseases Kinetochores Molecular Biology Interphase Centromere Protein F Chromosome Aberrations Mice Knockout Kinetochore Cell Cycle Microfilament Proteins Cell migration Cell Biology Cell cycle Fibroblasts Cell biology 030104 developmental biology Brief Reports sense organs Protein Binding |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | Genetic deletion of one microtubule-binding domain in CENP-F results in multiple cellular changes, including changes in cell migration, adhesion, and cilia formation. All of these changes are related to an increase in microtubule stabilization in CENP-F mutants. This suggests that CENP-F plays a role in microtubule organization outside of mitosis. 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. |
| Databáze: | OpenAIRE |
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