PRC1 cooperates with CLASP1 to organize central spindle plasticity in mitosis.
During cell division, chromosome segregation is governed by the interaction of spindle microtubules with the kinetochore. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution of cytokinesis. Central spindle organization requires mitotic kinesins, microtubule-bundling protein PRC1, and Aurora B kinase complex. However, the precise role of PRC1 in central spindle organization has remained elusive. Here we show that PRC1 recruits CLASP1 to the central spindle at early anaphase onset. CLASP1 belongs to a conserved microtubule-binding protein family that mediates the stabilization of overlapping microtubules of the central spindle. PRC1 physically interacts with CLASP1 and specifies its localization to the central spindle. Repression of CLASP1 leads to sister-chromatid bridges and depolymerization of spindle midzone microtubules. Disruption of PRC1-CLASP1 interaction by a membrane-permeable peptide abrogates accurate chromosome segregation, resulting in sister chromatid bridges. These findings reveal a key role for the PRC1-CLASP1 interaction in achieving a stable anti-parallel microtubule organization essential for faithful chromosome segregation. We propose that PRC1 forms a link between stabilization of CLASP1 association with central spindle microtubules and anti-parallel microtubule elongation.
Liu
Jing
J
Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China.
Wang
Zhikai
Z
Jiang
Kai
K
Zhang
Liangyu
L
Zhao
Lingli
L
Hua
Shasha
S
Yan
Feng
F
Yang
Yong
Y
Wang
Dongmei
D
Fu
Chuanhai
C
Ding
Xia
X
Guo
Zhen
Z
Yao
Xuebiao
X
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D020090:Chromosome Segregation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism*
C497850:CLASP1 protein, human; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C116662:PRC1 protein, human