Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America.
PLoS One. 2011;6(12):e28614. doi: 10.1371/journal.pone.0028614. Epub 2011 Dec 14.
Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173-220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120-140 are essential but not sufficient for LD enlargement, whereas amino acids 120-210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation.
脂肪特异性蛋白 27（FSP27）是脂肪细胞中与脂滴（LD）相关的蛋白，调节甘油三酯（TG）的储存。在本研究中，我们证明了 FSP27 在 LD 形态中起着关键作用，以积累 TG。我们在这里表明，FSP27 促进了 LD 的聚集，随后它们融合成更少和更大的液滴。为了确定 FSP27 负责这些事件的结构域，我们生成了 GFP 融合构建体的 FSP27 缺失突变体。显微镜分析显示，FSP27 的 173-220 个氨基酸对于 FSP27 靶向 LD 和初始液滴聚集都是必需且充分的。120-140 个氨基酸对于 LD 增大是必需但不充分的，而 120-210 个氨基酸对于 LD 的聚集和融合形成增大的液滴是必需且充分的。此外，我们发现 FSP27 介导的 LD 增大，而不是其聚集，与甘油三酯的积累有关。这些结果表明了一个模型，其中 FSP27 促进 LD 聚集，然后促进它们融合形成更大的液滴，这是两个离散的、连续的步骤，随后是甘油三酯的积累。
