Ibayashi Megumi, Tatsumi Takayuki, Tsukamoto Satoshi
Laboratory Animal and Bioresource Sciences Section, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
Division of Reproductive Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo 157-8535, Japan.
J Reprod Dev. 2024 Oct 1;70(5):296-302. doi: 10.1262/jrd.2024-023. Epub 2024 Jul 15.
Lipid droplets (LDs) are endoplasmic reticulum-derived organelles that store neutral lipids (mostly triglycerides and cholesterol esters) within a phospholipid monolayer and appear in most eukaryotic cells. Perilipins (PLINs, comprising PLIN1-5) are abundant LD-associated proteins with highly variable expression levels among tissues. Although PLINs are expressed in the mammalian ovaries, little is known about their subcellular localization and physiological functions. In this study, we investigated the localization of PLIN1-3 and their relationship with LD synthesis using mCherry-HPos reporter mice, thereby enabling the visualization of LD biogenesis in vivo. PLIN2 and PLIN3 were localized as puncta in granulosa cells with low levels of LD synthesis in developing follicles. This localization pattern was quite different from that of PLIN1, which was mainly localized in the theca and interstitial cells with high levels of LD synthesis. In the corpus luteum, where LD synthesis is highly induced, PLIN2 and PLIN3 are abundant in the particulate structures, whereas PLIN1 is poorly distributed. We also generated global Plin2-deficient mice using the CRSPR/Cas9 system and demonstrated that the lack of PLIN2 did not alter the distribution of PLIN1 and PLIN3 but unexpectedly induced LD enlargement in the corpus luteum. Collectively, our results suggest that the localization of PLIN1-3 is spatiotemporally regulated and that PLIN2 deficiency influences LD mobilization in the corpus luteum within the ovaries.
脂滴（LDs）是源自内质网的细胞器，在磷脂单层内储存中性脂质（主要是甘油三酯和胆固醇酯），存在于大多数真核细胞中。围脂滴蛋白（PLINs，包括PLIN1 - 5）是丰富的与脂滴相关的蛋白质，在不同组织中的表达水平差异很大。尽管PLINs在哺乳动物卵巢中表达，但对其亚细胞定位和生理功能知之甚少。在本研究中，我们使用mCherry - HPos报告基因小鼠研究了PLIN1 - 3的定位及其与脂滴合成的关系，从而能够在体内可视化脂滴的生物发生。PLIN2和PLIN3定位为发育卵泡中脂滴合成水平较低的颗粒细胞中的点状结构。这种定位模式与PLIN1有很大不同，PLIN1主要定位于脂滴合成水平较高的卵泡膜和间质细胞中。在高度诱导脂滴合成的黄体中，PLIN2和PLIN3在颗粒结构中丰富，而PLIN1分布较少。我们还使用CRSPR/Cas9系统构建了全身性Plin2基因敲除小鼠，并证明缺乏PLIN2不会改变PLIN1和PLIN3的分布，但出乎意料地诱导了黄体中脂滴的增大。总的来说，我们的结果表明PLIN1 - 3的定位受到时空调节，并且PLIN2缺乏会影响卵巢内黄体中的脂滴动员。
