Wei Yu-Xia, Wang Ya-Han, Yu Xiao-Ting, Hu Lin-Lin, Luo Xiao-Qiong, Sun Shao-Chen
Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Reproductive Medicine of Guangxi Medical and Health Key Discipline Construction Project, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.
Cell Commun Signal. 2025 Jan 2;23(1):2. doi: 10.1186/s12964-024-01997-w.
Leucine-rich repeat kinase 2 (LRRK2) is a ROCO family member which its mutation is closely related with Parkinson's disease, and LRRK2 is widely involved into the regulation of autophagy, vesicle transport and neuronal proliferation. However, the roles of LRRK2 during mammalian oocyte maturation are still largely unclear. In present study, we disturbed the activity of LRRK2 and showed its essential roles in porcine oocytes. We showed that LRRK2 stably expressed during oocyte maturation, and the loss of LRRK2 activity disturbed cumulus expansion and oocyte polar body extrusion, indicating its involvement into oocyte maturation. Further analysis indicated that LRRK2 was related with cytoskeleton dynamics since its inhibition caused spindle organization defect and chromosome misalignment, and both cytoplasmic and cortex actin decreased. Moreover, LRRK2 co-localized with mitochondria and its activity was essential for mitochondria distribution. Loss of LRRK2 activity altered the TMRE level, which ultimately induced ROS-related oxidative stress. Taken together, our data suggested the important roles of LRRK2 on mammalian oocyte maturation through its effects on cytoskeleton dynamics and mitochondria functions.
富含亮氨酸重复激酶2（LRRK2）是ROCO家族成员，其突变与帕金森病密切相关，并且LRRK2广泛参与自噬、囊泡运输和神经元增殖的调控。然而，LRRK2在哺乳动物卵母细胞成熟过程中的作用仍不清楚。在本研究中，我们干扰了LRRK2的活性，并显示了其在猪卵母细胞中的重要作用。我们发现LRRK2在卵母细胞成熟过程中稳定表达，LRRK2活性的丧失扰乱了卵丘扩展和卵母细胞极体排出，表明其参与卵母细胞成熟。进一步分析表明，LRRK2与细胞骨架动力学有关，因为其抑制导致纺锤体组织缺陷和染色体排列紊乱，并且细胞质和皮质肌动蛋白减少。此外，LRRK2与线粒体共定位，其活性对线粒体分布至关重要。LRRK2活性的丧失改变了TMRE水平，最终诱导了与活性氧相关的氧化应激。综上所述，我们的数据表明LRRK2通过影响细胞骨架动力学和线粒体功能对哺乳动物卵母细胞成熟具有重要作用。
