期刊
CELL CYCLE
卷 8, 期 20, 页码 3384-3395出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.20.9885
关键词
Astrin; meiotic maturation; spindle assembly; dominant negative; site-directed mutation
类别
资金
- National Basic Research Program of China [2006CB944001, 2006CB504004]
- National Natural Science Foundation of China [30570944]
- CAS [KSCX2-YW-R-52]
Astrin has been described as a microtubule and kinetochore protein required for the maintenance of sister chromatid cohesion and centrosome integrity in human mitosis. However, its role in mammalian oocyte meiosis is unclear. In this study, we find that Astrin is mainly associated with the meiotic spindle microtubules and concentrated on spindle poles at metaphase I and metaphase II stages. Taxol treatment and immunoprecipitation show that Astrin may interact with the centrosomal proteins Aurora-A or Plk1 to regulate microtubule organization and spindle pole integrity. Loss-of-function of Astrin by RNAi and overexpression of the coiled-coil domain results in spindle disorganization, chromosome misalignment and meiosis progression arrest. Thr24, Ser66 or Ser447 may be the potential phosphorylation sites of Astrin by Plk1, as site-directed mutation of these sites causes oocyte meiotic arrest at metaphase I with highly disordered spindles and disorganized chromosomes, although mutant Astrin localizes to the spindle apparatus. Taken together, these data strongly suggest that Astrin is critical for meiotic spindle assembly and maturation in mouse oocytes.
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