FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation.

FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation.
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DOI:
10.1371/journal.pone.0028614
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Puri V
Puri V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jambunathan S;Yin J;Khan W;Tamori Y;Puri V

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脂肪特异性蛋白27 (FSP27)是脂肪细胞中的脂滴(LD)相关蛋白,可调节甘油三酯(TG)的储存。在本研究中,我们证明FSP27在LD形态中起关键作用,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。为了绘制FSP27负责这些事件的结构域,我们生成了FSP27缺失突变体的gfp融合结构。显微镜分析表明,FSP27的173-220氨基酸对于FSP27靶向lld和液滴的初始聚集都是必要和充分的。氨基酸120-140对于LD的扩大是必需的,但不是足够的,而氨基酸120-210对于LD的聚集和融合形成扩大的液滴是必需的和足够的。此外,我们发现fsp27介导的ld增大,而不是它们的聚集,与甘油三酯积累有关。这些结果表明,在一个模型中,FSP27促进LD聚集,然后促进它们在两个离散的、连续的步骤中融合形成扩大的液滴,以及随后的甘油三酯积累。
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.
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