title: In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.
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.
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore.
authors.forename: Yoke-Peng
authors.initials: YP
authors.lastname: Lee
authors.forename: Chi-Hang
authors.initials: CH
authors.lastname: Wong
authors.forename: Kheng-Sze
authors.initials: KS
authors.lastname: Chan
authors.forename: Soak-Kuan
authors.initials: SK
authors.lastname: Lai
authors.forename: Cheng-Gee
authors.initials: CG
authors.lastname: Koh
authors.forename: Hoi-Yeung
authors.initials: HY
authors.lastname: Li
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D006224:Cricetinae; D031541:Fluorescence Resonance Energy Transfer; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D057809:HEK293 Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D018386:Kinetochores / Q000201:enzymology* / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D008677:Metaphase; D008870:Microtubules / Q000201:enzymology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D059008:Time-Lapse Imaging; D020931:ran GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*; D000097606:Exportin 1 Protein
chemical_list: D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D017228:Hepatocyte Growth Factor; D028884:Karyopherins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C062521:RCC1 protein, human; C082332:macrophage stimulating protein; C576921:AURKB protein, human; C576925:Aurkb protein, rat