Two kinesin-like Kin I family proteins in fission yeast regulate of metaphase and the on the establishment set of anaphase A

被引:126
作者
Garcia, MA [1 ]
Koonrugsa, N [1 ]
Toda, T [1 ]
机构
[1] London Res Inst, Cancer Res UK, Lab Cell Regulat, London WC2A 3PX, England
关键词
D O I
10.1016/S0960-9822(02)00761-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Metaphase is thought to be a force-equilibrium state of "tug of war," in which poleward forces are pulling kinetochores and counteracting the cohesive forces between the centromeres. Unlike conventional kinesins, members of the Kin I family are microtubule-depolymerizing enzymes, which are expected to be molecules that could generate poleward forces. Results: We have characterized mitotic roles of two Kin I homologs, KIp5 and KIp6, in fission yeast. KIp5 and Klp6 colocalize to the mitotic kinetochores and the spindle midzone. These two proteins form a heterocomplex, but not a homocomplex. Albeit not essential, both proteins are required for accurate chromosome segregation and normal morphology of interphase microtubules. Time-lapse live analysis using GFP-alpha-tubulin indicates that these mutants spend a much longer time (2-fold) in mitosis before the initiation of anaphase B. Further observation using kinetochore and centromere markers shows that, in these mutants, sister centromeres move back and forth between the two poles, indicating that entry into anaphase A is delayed. This is supported by live image analysis showing that Cut2 securin is retained during the prolonged mitosis. Furthermore, the mitotic extension is dependent upon the Mad2 spindle checkpoint. Conclusions: We discuss two models of Kin I function in fission yeast. One proposes that KIp5 and KIp6 are required for efficient capturing of kinetochores by the spindles, while the other proposes that they are required to generate tension upon kinetochore capturing. Kin 1, therefore, plays a fundamental role in the establishment of metaphase, probably by generating poleward forces at the kinetochores.
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页码:610 / 621
页数:12
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