论文成果
VPS34 governs oocyte developmental competence by regulating mito-autophagy-a novel insight into the significance of Rab7 activity and its subcellular location.
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发表刊物：
Advanced Science
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刊物所在地：
USA
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关键字：
autophagy,mitophagy,oocyte,retromer,VPS34
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摘要：
Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte‐specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2‐ to 4‐cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2‐cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS‐related GTP‐binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.
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全部作者：
Kehan Wang,Yuting Lin,Lu Wang,Xin Jin,Yuexin Qiu,Wenya Sun,Ling Zhang,Yan Sun,Xiaowei Dou,Shiming Luo,Youqiang Su,Qingyuan Sun
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第一作者：
Wenwen Liu
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论文类型：
Research Article
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通讯作者：
Wenpei Xiang,Feiyang Diao,Jing Li
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论文编号：
10.1002/advs.202308823
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卷号：
11
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期号：
41
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页面范围：
e2308823
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ISSN号：
2198-3844
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是否译文：
否
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发表时间：
2024-09-17
上一条：Pathogenic variants of TUBB8 cause oocyte spindle defects by disrupting with EB1-CAKP5 interactions and potential treatment targeting microtubule acetylation through HDAC6 inhibition.
下一条：Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin).
