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Arf 鸟嘌呤核苷酸交换因子 GBF1 活性丧失会扰乱小鼠卵母细胞中的细胞器动态。

Loss of Arf Guanine Nucleotide Exchange Factor GBF1 Activity Disturbs Organelle Dynamics in Mouse Oocytes.

机构信息

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing210095, China.

出版信息

Microsc Microanal. 2021 Apr;27(2):400-408. doi: 10.1017/S1431927620024885.

DOI:10.1017/S1431927620024885
PMID:33478608
Abstract

GBF1 [Golgi brefeldin A (BFA) resistance factor 1] is a member of the guanine nucleotide exchange factors Arf family. GBF1 localizes at the cis-Golgi and endoplasmic reticulum (ER)-Golgi intermediate compartment where it participates in ER-Golgi traffic by assisting in the recruitment of the coat protein COPI. However, the roles of GBF1 in oocyte meiotic maturation are still unknown. In the present study, we investigated the regulatory functions of GBF1 in mouse oocyte organelle dynamics. In our results, GBF1 was stably expressed during oocyte maturation, and GBF1 localized at the spindle periphery during metaphase I. Inhibiting GBF1 activity led to aberrant accumulation of the Golgi apparatus around the spindle. This may be due to the effects of GBF1 on the localization of GM130, as GBF1 co-localized with GM130 and inhibiting GBF1 induced condensation of GM130. Moreover, the loss of GBF1 activity affected the ER distribution and induced ER stress, as shown by increased GRP78 expression. Mitochondrial localization and functions were affected, as the mitochondrial membrane potential was altered. Taken together, these results suggest that GBF1 has wide-ranging effects on the distribution and functions of Golgi apparatus, ER, and mitochondria as well as normal polar body formation in mouse oocytes.

摘要

GBF1[高尔基布雷菲德菌素 A(BFA)抗性因子 1]是鸟嘌呤核苷酸交换因子 Arf 家族的成员。GBF1 定位于顺式高尔基体和内质网(ER)-高尔基体中间区,在那里它通过协助 COPI 衣壳蛋白的募集参与 ER-Golgi 运输。然而,GBF1 在卵母细胞减数分裂成熟中的作用仍不清楚。在本研究中,我们研究了 GBF1 在小鼠卵母细胞细胞器动力学中的调节功能。在我们的结果中,GBF1 在卵母细胞成熟过程中稳定表达,并在中期 I 时定位于纺锤体周围。抑制 GBF1 活性导致高尔基体在纺锤体周围异常积累。这可能是由于 GBF1 对 GM130 定位的影响,因为 GBF1 与 GM130 共定位,并且抑制 GBF1 诱导 GM130 的凝聚。此外,GBF1 活性的丧失影响 ER 分布并诱导 ER 应激,如 GRP78 表达增加所示。线粒体定位和功能受到影响,因为改变了线粒体膜电位。总之,这些结果表明 GBF1 对高尔基体、ER 和线粒体的分布和功能以及小鼠卵母细胞中正常极体形成有广泛的影响。

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