Abstract
Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aurora Kinase B
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Aurora Kinases
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Cell Cycle Proteins / metabolism
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Chromosomes, Mammalian / metabolism
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Cricetinae
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Exportin 1 Protein
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Fluorescence Resonance Energy Transfer
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Guanine Nucleotide Exchange Factors / metabolism
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HEK293 Cells
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Hepatocyte Growth Factor / metabolism
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Humans
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Karyopherins / metabolism
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Kinetochores / enzymology*
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Kinetochores / metabolism
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M Phase Cell Cycle Checkpoints
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Metaphase
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Microtubules / enzymology*
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Microtubules / metabolism
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Nuclear Proteins / metabolism
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Phosphorylation
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Protein Binding
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Protein Processing, Post-Translational
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Protein Serine-Threonine Kinases / metabolism*
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Protein Stability
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Proteolysis
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Proto-Oncogene Proteins / metabolism
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Rats
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Receptors, Cytoplasmic and Nuclear / metabolism
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Time-Lapse Imaging
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ran GTP-Binding Protein / metabolism
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ran GTP-Binding Protein / physiology*
Substances
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Cell Cycle Proteins
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Guanine Nucleotide Exchange Factors
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Karyopherins
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Nuclear Proteins
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Proto-Oncogene Proteins
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RCC1 protein, human
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Receptors, Cytoplasmic and Nuclear
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macrophage stimulating protein
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Hepatocyte Growth Factor
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AURKB protein, human
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Aurkb protein, rat
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Aurora Kinase B
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Aurora Kinases
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Protein Serine-Threonine Kinases
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ran GTP-Binding Protein
Grants and funding
This work was supported by Academic Research Council, Ministry of Education, Singapore (Academic Research Fund AcRF Tier 1, RG37/08) and A*STAR, Biomedical Research Council (BMRC grant 08/1/22/19/568). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.