title: HURP regulates chromosome congression by modulating kinesin Kif18A function.
abstract: Chromosome biorientation and congression during mitosis require precise control of microtubule dynamics [1-4]. The dynamics of kinetochore microtubules (K-MTs) are regulated by a variety of microtubule-associated proteins (MAPs) [4-9]. Recently, a MAP known as HURP (hepatoma upregulated protein) was identified [10-12]. During mitosis, Ran-guanosine 5'-triphosphate (RanGTP) releases HURP from the importin β inhibitory complex and allows it to localize to the kinetochore fiber (k-fiber) [12, 13]. HURP stabilizes k-fibers and promotes chromosome congression [12, 14, 15]. However, the molecular mechanism underlying the role of HURP in regulating chromosome congression remains elusive. Here, we show that overexpression of the N-terminal microtubule binding domain (1-278 aa, HURP(278)) of HURP induces a series of mitotic defects that mimic the effects of Kif18A depletion. In addition, coimmunoprecipitation and bimolecular fluorescence complementation assays identify Kif18A as a novel interaction partner of HURP. Furthermore, quantitative results from live-cell imaging analyses illustrate that HURP regulates Kif18A localization and dynamics at the plus end of K-MTs. Lastly, misaligned chromosomes in HURP(278)-overexpressing cells can be partially rescued by the overexpression of Kif18A. Our results demonstrate in part the regulatory mechanism for Kif18A during chromosome congression and provide new insights into the mechanism of chromosome movement at the metaphase plate.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore 117543.
authors.forename: Fan
authors.initials: F
authors.lastname: Ye
authors.forename: Lora
authors.initials: L
authors.lastname: Tan
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Lih-Wen
authors.initials: LW
authors.lastname: Deng
authors.forename: Maki
authors.initials: M
authors.lastname: Murata-Hori
authors.forename: Yih-Cherng
authors.initials: YC
authors.lastname: Liou
mesh_terms: D002877:Chromosomes, Human / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism / Q000502:physiology; D008870:Microtubules / Q000378:metabolism / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype
chemical_list: C465041:DLGAP5 protein, human; D009363:Neoplasm Proteins; C502735:KIF18A protein, human; D016547:Kinesins