Kif18B interacts with EB1 and controls astral microtubule length during mitosis

被引:75
作者
Stout, Jane R. [1 ]
Yount, Amber L. [2 ]
Powers, James A. [3 ]
LeBlanc, Chantal [1 ]
Ems-McClung, Stephanie C. [1 ]
Walczak, Claire E. [1 ]
机构
[1] Indiana Univ, Med Sci Program, Bloomington, IN 47405 USA
[2] Indiana Univ, Biochem Program, Bloomington, IN 47405 USA
[3] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
基金
美国国家卫生研究院;
关键词
ADENOMATOUS POLYPOSIS-COLI; KINESIN-RELATED PROTEIN; MITOTIC SPINDLE; MOTOR PROTEINS; TAIL DOMAIN; AURORA-B; SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONGRESSION; DYNAMIC INSTABILITY; LOCALIZATION SIGNAL;
D O I
10.1091/mbc.E11-04-0363
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Regulation of microtubule (MT) dynamics is essential for proper spindle assembly and organization. Kinesin-8 family members are plus-end-directed motors that modulate plus-end MT dynamics by acting as MT depolymerases or as MT plus-end capping proteins. In this paper, we show that the human kinesin-8 Kif18B functions during mitosis to control astral MT organization. Kif18B is a MT plus-tip-tracking protein that localizes to the nucleus in interphase and is enriched at astral MT plus ends during early mitosis. Knockdown of Kif18B caused spindle defects, resulting in an increased number and length of MTs. A yeast two-hybrid screen identified an interaction of the C-terminal domain of Kif18B with the plus-end MT-binding protein EB1. EB1 knockdown disrupted Kif18B targeting to MT plus ends, indicating that EB1/Kif18B interaction is physiologically important. This interaction is direct, as the far C-terminal end of Kif18B is sufficient for binding to EB1 in vitro. Overexpression of this domain is sufficient for plus-end MT targeting in cells; however, targeting is enhanced by the motor domain, which cooperates with the tail to achieve proper Kif18B localization at MT plus ends. Our results suggest that Kif18B is a new MT dynamics regulatory protein that interacts with EB1 to control astral MT length.
引用
收藏
页码:3070 / 3080
页数:11
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