Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation.
Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation.
复制标题
围Perilipin A对于脂解活化过程中激素敏感脂肪酶的易位至关重要。
DOI：
10.1083/jcb.200210169
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发表时间：
2003-06-23
影响因子：
7.8
通讯作者：
Londos, Constantine
中科院分区：
文献类型：
--
作者：
Sztalryd, Carole;Xu, Guoheng;Dorward, Heidi;Tansey, John T;Contreras, Juan A;Kimmel, Alan R;Londos, Constantine
脂肪细胞脂解激活的一个关键步骤是脂肪敏感脂肪酶（HSL）从细胞质转移到脂质储存液滴表面。与野生型小鼠的脂肪细胞相比，围脂蛋白缺失动物的脂肪细胞具有升高的脂解基础速率，但未能最大限度地响应脂解刺激。该缺陷位于β-肾上腺素能受体-腺苷酸环化酶复合物的下游。现在，我们表明，HSL是基本相关的脂滴表面在低水平的围脂蛋白空，但刺激易位从胞质到脂滴是不存在的脂肪细胞来源于胚胎成纤维细胞的围脂蛋白空小鼠。我们还通过引入GFP标记的HSL（有或没有围脂蛋白A）在非脂肪细胞中国仓鼠卵巢细胞系中重建了HSL易位反应。在激活蛋白激酶A时，HSL-GFP仅在表达完全可磷酸化的周脂蛋白A的细胞中易位到脂滴，证实了周脂蛋白是引发HSL易位反应所必需的。此外，在同时表达HSL和围脂蛋白A的中国仓鼠卵巢细胞中，这两种蛋白质协同产生比单独表达这两种蛋白质中任一种的细胞更快加速的脂解，表明脂解是由蛋白激酶A磷酸化的HSL和围脂蛋白A介导的协同反应。
Akey step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin-null animals have an elevated basal rate of lipolysis compared with adipocytes from wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the β-adrenergic receptor–adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in perilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of perilipin-null mice. We have also reconstructed the HSL translocation reaction in the nonadipocyte Chinese hamster ovary cell line by introduction of GFP-tagged HSL with and without perilipin A. On activation of protein kinase A, HSL-GFP translocates to lipid droplets only in cells that express fully phosphorylatable perilipin A, confirming that perilipin is required to elicit the HSL translocation reaction. Moreover, in Chinese hamster ovary cells that express both HSL and perilipin A, these two proteins cooperate to produce a more rapidly accelerated lipolysis than do cells that express either of these proteins alone, indicating that lipolysis is a concerted reaction mediated by both protein kinase A–phosphorylated HSL and perilipin A.