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Mitotic kinesin CENP‐E cooperates with microtubule‐bundling protein PRC1 in temporal control of central spindle assembly (801.2)
Author(s) -
Liu Xing,
Yao Phil,
Wang Wenwen,
Qin Bo,
Dou Zhen,
Ding Xia,
Yao Xuebiao
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.801.2
Subject(s) - kinetochore , microbiology and biotechnology , mitosis , spindle pole body , spindle checkpoint , spindle apparatus , microtubule , aurora b kinase , kinesin , multipolar spindles , astral microtubules , mitotic exit , biology , metaphase , chromosome segregation , centromere , chemistry , cell division , genetics , chromosome , cell , gene
Chromosome movements during mitosis are orchestrated primarily by the interaction of spindle microtubules with the kinetochore, the site for attachment of spindle microtubules to the centromere. Kinetochore‐associated mitotic kinesin CENP‐E plays key roles in chromosome congression and spindle checkpoint satisfaction. We have recently identified and characterized syntelin, a novel selective CENP‐E inhibitor (Ding et al., 2010. Cell Res. 20, 1386‐1390). Cells treated with syntelin progress through interphase, enter mitosis normally with a bipolar spindle and lagging chromosomes around the poles. Syntelin is an allosteric inhibitor which tightens CENP‐E‐microtubule interaction by slowing inorganic phosphate release. To delineate the role of CENP‐E in reorganization of interpolar microtubules into an organized central spindle, metaphase synchronized cells were exposed to syntelin and other mitotic motor inhibitors. Syntelin does not perturb interpolar microtubule assembly but abrogates the anti‐parallel microtubule bundle formation. Real‐time image shows that CENP‐E inhibited cells undergo central spindle splitting and exhibits chromosome instability phenotypes. Interestingly, inhibition of CENP‐E did not alter the interaction between CENP‐E and PRC1 but perturbed temporal assembly of PRC1 to the midzone. Surprisingly, inhibition of CENP‐E perturbs the temporal control of PRC1 dephosphorylation which led to a persistent phosphorylation of PRC1 and an inhibition of central spindle assembly. These findings reveal a previously uncharacterized role of CENP‐E motor in temporal control of central spindle assembly. Grant Funding Source : DK56292; CA164133