You Seung Yeop, Park Yong Seok, Jeon Hyuk-Joon, Cho Dong-Hyung, Jeon Hong Bae, Kim Sung Hyun, Chang Jong Wook, Kim Jae-Sung, Oh Jeong Su
a Department of Genetic Engineering , College of Biotechnology and Bioengineering, Sungkyunkwan University , Suwon , Gyeonggi-do , Korea.
b Department of East-West Medical Science , Graduate School of East-West Medical Science, Kyung Hee University , Yongin , Korea.
Cell Cycle. 2016 Jun 17;15(12):1611-9. doi: 10.1080/15384101.2016.1181235. Epub 2016 May 5.
Cytokinesis is the final step in cell division that results in the separation of a parent cell into daughter cells. Unlike somatic cells that undergo symmetric division, meiotic division is highly asymmetric, allowing the preservation of maternal resources for embryo development. Beclin-1/BECN1, the mammalian homolog of yeast Atg6, is a key molecule of autophagy. As part of a class III phosphatidylinositol 3-kinase (PI3K-III) complex, BECN1 initiates autophagosome formation by coordinating membrane trafficking. However, emerging evidence suggests that BECN1 regulates chromosome segregation and cytokinesis during mitosis. Thus, we investigated the function of BECN1 during oocyte meiotic maturation. BECN1 was widely distributed during meiotic maturation forming small vesicles. Interestingly, BECN1 is also detected at the midbody ring during cytokinesis. Depletion of BECN1 impaired the cytokinetic abscission, perturbing the recruitment of ZFYVE26 at the midbody. Similar phenotypes were observed when PI3K-III activity was inhibited. However, inhibition of autophagy by depleting Atg14L did not disturb meiotic maturation. Therefore, our results not only demonstrate that BECN1 as a PI3K-III component is essential for cytokinesis, but also suggest that BECN1 is not associated with autophagy pathway in mouse oocytes.
胞质分裂是细胞分裂的最后一步,导致亲代细胞分离为子代细胞。与经历对称分裂的体细胞不同,减数分裂是高度不对称的,从而使母体资源得以保留用于胚胎发育。Beclin-1/BECN1是酵母Atg6的哺乳动物同源物,是自噬的关键分子。作为III类磷脂酰肌醇3激酶(PI3K-III)复合物的一部分,BECN1通过协调膜运输启动自噬体形成。然而,新出现的证据表明,BECN1在有丝分裂期间调节染色体分离和胞质分裂。因此,我们研究了BECN1在卵母细胞减数分裂成熟过程中的功能。BECN1在减数分裂成熟过程中广泛分布,形成小泡。有趣的是,在胞质分裂期间的中体环处也检测到BECN1。BECN1的缺失损害了胞质分裂切割,扰乱了ZFYVE26在中体处的募集。当PI3K-III活性受到抑制时,观察到类似的表型。然而,通过耗尽Atg14L抑制自噬并不干扰减数分裂成熟。因此,我们的结果不仅证明BECN1作为PI3K-III的一个组分对胞质分裂至关重要,而且还表明BECN1与小鼠卵母细胞中的自噬途径无关。