Poly（ADP-ribose） mediates asymmetric division of mouse oocyte  

作　　者：Bingteng Xie Lu Zhang Huiling Zhao Qingyun Bai Yong Fan Xiaohui Zhu Yang Yu Rong Li Xin Liang Qing-Yuan Sun Mo Li Jie Qiao 

机构地区：[1]Center for Reproductive Medicine, Peking University Third Hospital, 100191 Beijing, China [2]Key Laboratory of Assisted Reproduction, Ministry of Education, 100191 Beijing, China [3]School of Basic Medical Sciences, Peking University Health Science Center, 100191 Beijing, China [4]Key Laboratory for Major Obstetric Diseases of Guangdong Province The Third Affiliated Hospital of Guangzhou Medical University, 510150 Guangzhou, China [5]Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University,100084 Beijing, China [6]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China

出　　处：《Cell Research》2018年第4期462-475,共14页细胞研究（英文版）

基　　金：We are grateful to Dr. Bo Xiong for the insightful comments and suggestions on the manuscript. This work was supported by the grants from ＂Reproductive health and major birth defects prevention and control research＂ of Key Special Fund （2016YFCI000604）, ＂Mechanism and clinical application of oocyte in vitro maturation＂ of Key Special Fund （2017YFCI001501）, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China （81521002）. M. L. is a member of Thousand Young Talents Program of China,

摘　　要：Before fertilization, mammalian oocyte undergoes an asymmetric division which depends on eccentric positioning of the spindle at the oocyte cortex to form a polar body and an egg. Since the centriole is absent and, as a result, the polar array microtubules are not fully developed in oocytes, microtubules have seldom been considered as required for eccentric positioning of the spindle, while actin-related forces have instead been proposed to be primarily responsible for this process. However, the existing models are largely conflicting and the underlying mechanism of asymmetric division is still elusive. Here we show that poly（ADP-ribose） （PAR） is enriched at mouse oocyte cortical area throughout meiosis. Specific removal of cortical PAR results in an ectopic spindle and a failure of asymmetric division. During spindle migration, when the spindle deviates from the center of oocyte by a pushing force of cytoplasmic actin, the short polar array microtubules emanating from the juxtacortical spindle pole extend to the cortex and penetrate into cortical PAR, docking and stabilizing the spindle at the cortex which facilitates the asymmetric division. This process depends on the affinity between PAR and microtubule-associated proteins such as Spindly, which contributes to a physical link for cortical PAR and the spindle. Notably, fusing a PAR-binding domain to end-binding protein 3, a plus-end tracking protein at the polar array microtubules, restores the asymmetric division of oocytes with Spindly knockdown. Thus, our work demonstrates a comprehensive mechanism for oocyte spindle positioning and asymmetric division.

关 键 词：MEIOSIS PolyADP-ribosylation 

分 类 号：TP317.4[自动化与计算机技术—计算机软件与理论] Q492.5[自动化与计算机技术—计算机科学与技术]