Perilipin Controls Lipolysis by Regulating the Interactions of AB-hydrolase Containing 5 (Abhd5) and Adipose Triglyceride Lipase (Atgl)
Perilipin Controls Lipolysis by Regulating the Interactions of AB-hydrolase Containing 5 (Abhd5) and Adipose Triglyceride Lipase (Atgl)
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DOI：
10.1074/jbc.m109.068478
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发表时间：
2009-12-11
影响因子：
4.8
通讯作者：
Rathod, Miloni
中科院分区：
文献类型：
--
作者：
Granneman, James G.;Moore, Hsiao-Ping H.;Rathod, Miloni
通过激素动员储存的脂质是脂肪细胞的基本功能，并且有强有力的证据表明，脂滴支架perilipin（Plin）和脂肪组织甘油三酯脂肪酶（Atgl）（一种磷脂酰胆碱特异性脂肪酶）发挥关键作用。以前的工作表明，Abhd 5，Atgl的蛋白激活剂，协调与Plin控制基础和刺激的脂解;然而，潜在的机制是有争议的。本实验研究活细胞中Plin、Atgl和Abhd 5之间的蛋白质运输和相互作用。结果表明Plin以高亲和力结合Abhd 5，从而抑制Abhd 5与Atgl的相互作用。Abhd 5的隔离似乎是Plin减少基础脂解的主要机制。Plin在丝氨酸492或丝氨酸517上的磷酸化从Plin快速释放Abhd 5，允许Abhd 5直接与Atgl相互作用。成像实验证明Abhd 5和Atgl的Plin依赖性相互作用主要但不排他地发生在含有Plin的脂滴上。
The mobilization of stored lipid by hormones is a fundamental function of fat cells, and there is strong evidence that perilipin (Plin), a lipid droplet scaffold, and adipose tissue triglyceride lipase (Atgl), a triglyceride-specific lipase, play critical roles. Previous work suggested that Abhd5, a protein activator of Atgl, coordinates with Plin in controlling basal and stimulated lipolysis; however, the underlying mechanism is controversial. The present experiments investigated protein trafficking and interactions among Plin, Atgl, and Abhd5 in live cells. The results demonstrate that Plin binds Abhd5 with high affinity and thereby suppresses the interaction of Abhd5 with Atgl. Sequestration of Abhd5 appears to a major mechanism by which Plin reduces basal lipolysis. Phosphorylation of Plin on serine 492 or serine 517 rapidly releases Abhd5 from Plin, allowing Abhd5 to directly interact with Atgl. Imaging experiments demonstrated that the Plin-dependent interaction of Abhd5 and Atgl occurs mainly, but not exclusively, on lipid droplets that contain Plin.