Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, The National Institutes of Health, Bethesda, MD 20892, USA.
J Cell Sci. 2012 Sep 1;125(Pt 17):4067-76. doi: 10.1242/jcs.104943. Epub 2012 Jun 8.
Perilipin family proteins (Plins) coat the surface of intracellular neutral lipid storage droplets in various cell types. Studies across diverse species demonstrate that Plins regulate lipid storage metabolism through recruitment of lipases and other regulatory proteins to lipid droplet surfaces. Mammalian genomes have distinct Plin gene members and additional protein forms derived from specific mRNA splice variants. However, it is not known if the different Plins have distinct functional properties. Using biochemical, cellular imaging and flow cytometric analyses, we now show that within individual cells of various types, the different Plin proteins preferentially sequester to separate pools of lipid storage droplets. By examining ectopically expressed GFP fusions and all endogenous Plin protein forms, we demonstrate that different Plins sequester to different types of lipid droplets that are composed of either triacylcerides or cholesterol esters. Furthermore, Plins with strong association preferences to triacylceride (or cholesterol ester) droplets can re-direct the relative intracellular triacylceride-cholesterol ester balance toward the targeted lipid. Our data suggest diversity of Plin function, alter previous assumptions about shared collective actions of the Plins, and indicate that each Plin can have separate and unique functions.
脂滴相关蛋白家族（Plin）家族蛋白覆盖在各种细胞类型的细胞内中性脂质储存滴的表面。跨不同物种的研究表明，Plin 通过招募脂肪酶和其他调节蛋白到脂滴表面来调节脂质储存代谢。哺乳动物基因组具有不同的 Plin 基因成员和特定 mRNA 剪接变体衍生的额外蛋白形式。然而，不同的 Plin 是否具有不同的功能特性尚不清楚。我们现在使用生化、细胞成像和流式细胞术分析表明，在不同类型的单个细胞中，不同的 Plin 蛋白优先隔离到不同的脂质储存滴池。通过检查异位表达的 GFP 融合蛋白和所有内源性 Plin 蛋白形式，我们证明不同的 Plin 隔离到不同类型的由三酰甘油或胆固醇酯组成的脂滴。此外，与三酰甘油（或胆固醇酯）滴具有强结合偏好的 Plin 可以将相对细胞内三酰甘油-胆固醇酯平衡重新定向到靶向脂质。我们的数据表明 Plin 功能的多样性，改变了以前对 Plin 共同集体作用的假设，并表明每个 Plin 都可以具有单独且独特的功能。
