perilipin1 通过激活脂肪细胞中的 Fsp27 促进单泡脂滴形成。
Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes.
机构信息
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
出版信息
Nat Commun. 2013;4:1594. doi: 10.1038/ncomms2581.
Mature white adipocytes contain a characteristic unilocular lipid droplet. However, the molecular mechanisms underlying unilocular lipid droplet formation are poorly understood. We previously showed that Fsp27, an adipocyte-specific lipid droplet-associated protein, promotes lipid droplet growth by initiating lipid exchange and transfer. Here, we identify Perilipin1 (Plin1), another adipocyte-specific lipid droplet-associated protein, as an Fsp27 activator. Plin1 interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth. Functional cooperation between Plin1 and Fsp27 is required for efficient lipid droplet growth in adipocytes, as depletion of either protein impairs lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers and disruption of CIDE-N homodimerization abolishes Fsp27-mediated lipid exchange and transfer. Interestingly, Plin1 can restore the activity of CIDE-N homodimerization-defective mutants of Fsp27. We thus uncover a novel mechanism underlying lipid droplet growth and unilocular lipid droplet formation that involves the cooperative action of Fsp27 and Plin1 in adipocytes.
成熟的白色脂肪细胞含有特征性的单房性脂滴。然而，单房性脂滴形成的分子机制还知之甚少。我们之前的研究表明，脂肪细胞特异性脂滴相关蛋白 Fsp27 通过启动脂滴交换和转移来促进脂滴生长。在这里，我们鉴定出另一种脂肪细胞特异性脂滴相关蛋白 Perilipin1（Plin1）是 Fsp27 的激活剂。Plin1 与 Fsp27 的 CIDE-N 结构域相互作用，并显著增加 Fsp27 介导的脂交换、脂转移和脂滴生长。Plin1 和 Fsp27 之间的功能合作是脂肪细胞中有效脂滴生长所必需的，因为两种蛋白质的消耗都会损害脂滴生长。Fsp27 的 CIDE-N 结构域形成同源二聚体，破坏 CIDE-N 同源二聚体化会消除 Fsp27 介导的脂交换和转移。有趣的是，Plin1 可以恢复 Fsp27 同源二聚体缺陷突变体的活性。因此，我们揭示了一种涉及脂肪细胞中 Fsp27 和 Plin1 协同作用的脂滴生长和单房性脂滴形成的新机制。
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