title: Phosphorylation of SKAP by GSK3β ensures chromosome segregation by a temporal inhibition of Kif2b activity.
abstract: Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent study shows SKAP is an EB1-dependent, microtubule plus-end tracking protein essential for kinetochore oscillations during mitosis. Here we show that phosphorylation of SKAP by GSK3β regulates Kif2b depolymerase activity by competing Kif2b for microtubule plus-end binding. SKAP is a bona fide substrate of GSK3β in vitro and the phosphorylation is essential for an accurate kinetochore-microtubule attachment in cells. The GSK3β-elicited phosphorylation sites were mapped by mass spectrometry and the phosphomimetic mutant of SKAP can rescue the phenotype of chromosome missegregation in SKAP-suppressed cells. Importantly, GSK3β-elicited phosphorylation promotes SKAP binding to Kif2b to regulate its depolymerase activity at the microtubule plus-ends. Based on those findings, we reason that GSK3β-SKAP-Kif2b signaling axis constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Mo
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.
authors.forename: Hengyi
authors.initials: H
authors.lastname: Shao
authors.affiliation: Molecular Imaging Center, Atlanta Clinical &Translational Science Institute, Atlanta, GA 30310.
authors.forename: Jane
authors.initials: J
authors.lastname: Chu
authors.affiliation: Molecular Imaging Center, Atlanta Clinical &Translational Science Institute, Atlanta, GA 30310.
authors.forename: Michael
authors.initials: M
authors.lastname: Powell
authors.affiliation: Molecular Imaging Center, Atlanta Clinical &Translational Science Institute, Atlanta, GA 30310.
authors.forename: Felix
authors.initials: F
authors.lastname: Aikhionbare
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.|Center of Excellence on Molecular Cell Sciences, Chinese Academy of Sciences, Hefei 230026, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.|Center of Excellence on Molecular Cell Sciences, Chinese Academy of Sciences, Hefei 230026, China.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Pan
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.|Center of Excellence on Molecular Cell Sciences, Chinese Academy of Sciences, Hefei 230026, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.|Center of Excellence on Molecular Cell Sciences, Chinese Academy of Sciences, Hefei 230026, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science &Technology of China, Hefei 230027, China.|Center of Excellence on Molecular Cell Sciences, Chinese Academy of Sciences, Hefei 230026, China.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C523507:KIF2B protein, human; D016547:Kinesins