GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes
GTPase-activating protein Elmod2 is essential for meiotic progression in mouse oocytes
复制标题
GTP酶激活蛋白Elmod2对于小鼠卵母细胞减数分裂进程至关重要
DOI：
10.1080/15384101.2017.1304329
复制
发表时间：
2017-03
期刊：
影响因子：
4.3
通讯作者：
Dong Zhang
中科院分区：
文献类型：
--
作者：
Chun-Xiang Zhou;Li-Ya Shi;Rui-Chao Li;Ya-Hong Liu;Bo-Qun Xu;Jin-Wei Liu;Bo Yuan;Zhi-Xia Yang;Xiao-Yan Ying;Dong Zhang
卵母细胞减数分裂失败是人类受精卵源性生殖疾病的主要决定因素，减数分裂的成功完成在很大程度上依赖于女性生育因子的正常功能。Elmod 2是Elmod家族中具有最强GAP（GTP酶激活蛋白）活性的成员;尽管它被鉴定为可能的母体蛋白，但其在哺乳动物卵母细胞中的实际生理作用尚未阐明。在Elmod家族蛋白中，Elmod 2在小鼠卵母细胞中含量最高，特异性siRNA抑制Elmod 2可导致减数分裂严重延迟和分裂后期染色体分离异常。Elmod 2敲低也显著降低了卵母细胞成熟（至MII，伴随第一极体排出）的速率，并且显著更大数量的Elmod 2敲低的MII卵母细胞是非整倍体。相应地，Elmod 2敲除显著降低了受精率。为了研究所涉及的机制，我们发现Elmod 2敲低导致显著更多的异常线粒体聚集和细胞ATP水平降低;并且我们还发现Elmod 2与Arl 2共定位并相互作用，Arl 2是一种已知维持卵母细胞中线粒体动力学和ATP水平的GT3。总之，我们发现Elmod 2是小鼠卵母细胞减数分裂进程所必需差距，最有可能通过调节线粒体动力学。
ABSTRACT Meiotic failure in oocytes is the major determinant of human zygote-originated reproductive diseases, the successful accomplishment of meiosis largely relay on the normal functions of many female fertility factors. Elmod2 is a member of the Elmod family with the strongest GAP (GTPase-activating protein) activity; although it was identified as a possible maternal protein, its actual physiologic role in mammalian oocytes has not been elucidated. Herein we reported that among Elmod family proteins, Elmod2 is the most abundant in mouse oocytes, and that inhibition of Elmod2 by specific siRNA caused severe meiotic delay and abnormal chromosomal segregation during anaphase. Elmod2 knockdown also significantly decreased the rate of oocyte maturation (to MII, with first polar body extrusion), and significantly greater numbers of Elmod2-knockdown MII oocytes were aneuploid. Correspondingly, Elmod2 knockdown dramatically decreased fertilization rate. To investigate the mechanism(s) involved, we found that Elmod2 knockdown caused significantly more abnormal mitochondrial aggregation and diminished cellular ATP levels; and we also found that Elmod2 co-localized and interacted with Arl2, a GTPase that is known to maintain mitochondrial dynamics and ATP levels in oocytes. In summary, we found that Elmod2 is the GAP essential to meiosis progression of mouse oocytes, most likely by regulating mitochondrial dynamics.
登录
查看更多内容
小GTPase ARF6在癌症进展中的病理功能：肿瘤血管生成和转移。
影响因子：
--
作者：
Hongu T;Yamauchi Y;Funakoshi Y;Katagiri N;Ohbayashi N;Kanaho Y
通讯作者：
Kanaho Y
影响因子：
44.1
作者：
Xiao Zhang;Xue-qing Wu;Shuang Lu;Ying Guo;Xu Ma
通讯作者：
Xiao Zhang;Xue-qing Wu;Shuang Lu;Ying Guo;Xu Ma
影响因子：
4.8
作者：
Ivanova, Anna A.;East, Michael P.;Kahn, Richard A.
通讯作者：
Kahn, Richard A.
影响因子：
5.6
作者：
Dalton, Caroline M.;Szabadkai, Gyorgy;Carroll, John
通讯作者：
Carroll, John
影响因子：
4.8
作者：
Ma, Rujun;Hou, Xiaojing;Wang, Qiang
通讯作者：
Wang, Qiang