Thomalla Jonathon M, Giedt Michelle S, White Roger P, Wipf Israel J, Shipley Alicia, Chen Minhao, Welte Michael A, Tootle Tina L
Department of Molecular Biology and Genetics, Cornell University, Ithaca 14853, NY.
Department of Biology, University of Rochester, Rochester 14627, NY.
Mol Biol Cell. 2025 Sep 1;36(9):ar105. doi: 10.1091/mbc.E25-05-0218. Epub 2025 Jul 9.
Growing evidence supports that lipid droplets (LD) are critical for producing high-quality oocytes. However, the functions of LDs during oocyte development remain largely unknown. Using oogenesis as a model, we previously discovered that the LD-associated Adipose Triglyceride Lipase (ATGL) promotes actin remodeling necessary for oocyte development by providing the substrate for producing lipid signals termed prostaglandins (PG). Here, we find that Jabba, a LD-associated protein best known for its role in anchoring other proteins to LDs, also promotes PG-dependent actin remodeling. Overexpression of Jabba results in thickened cortical actin and excessive actin bundles, whereas loss of Jabba results in cortical actin breakdown and severely defective actin bundle formation. We find that Jabba regulates actin remodeling in conjunction with PG signaling. However, the lack of a genetic interaction between Jabba and ATGL suggests the PG-Jabba pathway is independent of ATGL. These data are consistent with the model that there are multiple PG signaling pathways promoting actin remodeling. Overexpression of Jabba rescues the actin defects when PG signaling is lost. Together, these data lead to the model that PGs produced independently of ATGL positively regulate Jabba to promote actin remodeling necessary for follicle morphogenesis.
越来越多的证据支持脂滴(LD)对于产生高质量卵母细胞至关重要。然而,脂滴在卵母细胞发育过程中的功能仍 largely 未知。以卵子发生为模型,我们先前发现与脂滴相关的脂肪甘油三酯脂肪酶(ATGL)通过为产生称为前列腺素(PG)的脂质信号提供底物,促进卵母细胞发育所需的肌动蛋白重塑。在这里,我们发现 Jabba,一种以其在将其他蛋白质锚定到脂滴中的作用而闻名的与脂滴相关的蛋白质,也促进依赖 PG 的肌动蛋白重塑。Jabba 的过表达导致皮质肌动蛋白增厚和过多的肌动蛋白束,而 Jabba 的缺失导致皮质肌动蛋白分解和严重缺陷的肌动蛋白束形成。我们发现 Jabba 与 PG 信号传导一起调节肌动蛋白重塑。然而,Jabba 和 ATGL 之间缺乏遗传相互作用表明 PG-Jabba 途径独立于 ATGL。这些数据与存在多种促进肌动蛋白重塑的 PG 信号传导途径的模型一致。当 PG 信号传导丧失时,Jabba 的过表达挽救了肌动蛋白缺陷。总之,这些数据导致这样的模型,即独立于 ATGL 产生的 PG 正向调节 Jabba 以促进卵泡形态发生所需的肌动蛋白重塑。