Mad1 promotes chromosome congression by anchoring a kinesin motor to the kinetochore

被引:48
作者
Akera, Takashi [1 ,2 ]
Goto, Yuhei [1 ,2 ]
Sato, Masamitsu [2 ]
Yamamoto, Masayuki [2 ]
Watanabe, Yoshinori [1 ,2 ]
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Chromosome Dynam, Tokyo 1130032, Japan
[2] Univ Tokyo, Grad Program Biophys & Biochem, Grad Sch Sci, Tokyo 1130032, Japan
关键词
SPINDLE-ASSEMBLY CHECKPOINT; FISSION YEAST; CELL-CYCLE; CENP-E; PHOSPHORYLATION; MICROTUBULES; BUB1; ATTACHMENT; PROTEINS; GENE;
D O I
10.1038/ncb3219
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
For proper partitioning of genomes in mitosis, all chromosomes must be aligned at the spindle equator before the onset of anaphase. The spindle assembly checkpoint (SAC) monitors this process, generating a 'wait anaphase' signal at unattached kinetochores of misaligned chromosomes. However, the link between SAC activation and chromosome alignment is poorly understood. Here we show that Mad1, a core SAC component, plays a hitherto concealed role in chromosome alignment. Protein-protein interaction screening revealed that fission yeast Mad1 binds the plus-end-directed kinesin-5 motor protein Cut7 (Eg5 homologue), which is generally thought to promote spindle bipolarity. We demonstrate that Mad1 recruits Cut7 to kinetochores of misaligned chromosomes and promotes chromosome gliding towards the spindle equator. Similarly, human Mad1 recruits another kinetochore motor CENP-E, revealing that Mad1 is the conserved dual-function protein acting in SAC activation and chromosome gliding. Our results suggest that the mitotic checkpoint has co-evolved with a mechanism to drive chromosome congression.
引用
收藏
页码:1124 / +
页数:21
相关论文
共 56 条
  • [1] The bipolar assembly domain of the mitotic motor kinesin-5
    Acar, Seyda
    Carlson, David B.
    Budamagunta, Madhu S.
    Yarov-Yarovoy, Vladimir
    Correia, John J.
    Ninonuevo, Milady R.
    Jia, Weitao
    Tao, Li
    Leary, Julie A.
    Voss, John C.
    Evans, James E.
    Scholey, Jonathan M.
    [J]. NATURE COMMUNICATIONS, 2013, 4
  • [2] Bähler J, 1998, YEAST, V14, P943, DOI 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO
  • [3] 2-Y
  • [4] Microtubule detyrosination guides chromosomes during mitosis
    Barisic, Marin
    Silva e Sousa, Ricardo
    Tripathy, Suvranta K.
    Magiera, Maria M.
    Zaytsev, Anatoly V.
    Pereira, Ana L.
    Janke, Carsten
    Grishchuk, Ekaterina L.
    Maiato, Helder
    [J]. SCIENCE, 2015, 348 (6236) : 799 - 803
  • [5] Kinetochore motors drive congression of peripheral polar chromosomes by overcoming random arm-ejection forces
    Barisic, Marin
    Aguiar, Paulo
    Geley, Stephan
    Maiato, Helder
    [J]. NATURE CELL BIOLOGY, 2014, 16 (12) : 1249 - U259
  • [6] Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis
    Bernard, P
    Hardwick, K
    Javerzat, JP
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 143 (07) : 1775 - 1787
  • [7] Phosphorylation by p34(cdc2) regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo
    Blangy, A
    Lane, HA
    dHerin, P
    Harper, M
    Kress, M
    Nigg, EA
    [J]. CELL, 1995, 83 (07) : 1159 - 1169
  • [8] Chromosome congression in the absence of kinetochore fibres
    Cai, Shang
    O'Connell, Christopher B.
    Khodjakov, Alexey
    Walczak, Claire E.
    [J]. NATURE CELL BIOLOGY, 2009, 11 (07) : 832 - U118
  • [9] Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1
    Chan, GKT
    Schaar, BT
    Yen, TJ
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 143 (01) : 49 - 63
  • [10] Prime movers: the mechanochemistry of mitotic kinesins
    Cross, Robert A.
    McAinsh, Andrew
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (04) : 257 - 271