title: Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Elise R
authors.initials: ER
authors.lastname: Pfaltzgraff
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Roth
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Miller
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232.
authors.forename: Anneelizabeth G
authors.initials: AG
authors.lastname: Gintzig
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232 ryoma.ohi@vanderbilt.edu david.bader@vanderbilt.edu.
authors.forename: Ryoma
authors.initials: R
authors.lastname: Ohi
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232 ryoma.ohi@vanderbilt.edu david.bader@vanderbilt.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Bader
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D005347:Fibroblasts; D007399:Interphase / Q000235:genetics; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology; D008938:Mitosis / Q000235:genetics; D011485:Protein Binding
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; C094772:centromere protein F