title: NuSAP modulates the dynamics of kinetochore microtubules by attenuating MCAK depolymerisation activity.
abstract: Nucleolar and spindle-associated protein (NuSAP) is a microtubule-associated protein that functions as a microtubule stabiliser. Depletion of NuSAP leads to severe mitotic defects, however the mechanism by which NuSAP regulates mitosis remains elusive. In this study, we identify the microtubule depolymeriser, mitotic centromere-associated kinesin (MCAK), as a novel binding partner of NuSAP. We show that NuSAP regulates the dynamics and depolymerisation activity of MCAK. Phosphorylation of MCAK by Aurora B kinase, a component of the chromosomal passenger complex, significantly enhances the interaction of NuSAP with MCAK and modulates the effects of NuSAP on the depolymerisation activity of MCAK. Our results reveal an underlying mechanism by which NuSAP controls kinetochore microtubule dynamics spatially and temporally by modulating the depolymerisation function of MCAK in an Aurora B kinase-dependent manner. Hence, this study provides new insights into the function of NuSAP in spindle formation during mitosis.
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
authors.forename: Fan
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.
authors.forename: Stella Ying
authors.initials: SY
authors.lastname: Sun
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Republic of Singapore.
authors.forename: Ee Sin
authors.initials: ES
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, 117543, Republic of Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117573, Republic of Singapore.
authors.forename: Yih-Cherng
authors.initials: YC
authors.lastname: Liou
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D055550:Protein Stability
chemical_list: C091489:KIF2C protein, human; D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D016547:Kinesins