Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control.
Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control.
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DOI：
10.1194/jlr.ra120001126
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发表时间：
2021
影响因子：
6.5
通讯作者：
Watt MJ
中科院分区：
文献类型：
--
作者：
Keenan SN;De Nardo W;Lou J;Schittenhelm RB;Montgomery MK;Granneman JG;Hinde E;Watt MJ
Perilipin 5(PLIN5)是一种脂滴相关蛋白，在高度氧化的组织中协调细胞内的脂解作用，并被认为调节蛋白激酶A(PKA)的磷酸化反应中的脂代谢。我们试图确定PLIN5中的PKA磷酸化位点，并评估它们在培养细胞和小鼠肝脏中的功能相关性。我们检测到S155上的磷酸化，并确定S155是脂类代谢的重要功能位点。在Plin5缺失细胞中表达磷酸化缺陷的PLIN5 S155A导致脂肪分解和甘油三酯衍生脂肪酸氧化的比率降低。蛋白质相互作用的Flim-FRET分析表明，PLIN5S155磷酸化调节PLIN5与脂滴上的脂肪甘油三酯脂酶的相互作用，但不调节含有α-β水解酶结构域的PLIN5S155A的相互作用。与野生型PLIN5S155相比，PLIN5S155A在肝脏中的重新表达减少了脂解作用，但与肝脂代谢的其他变化无关。此外，与表达PLIN5的小鼠相比，表达PLIN5 S155A的小鼠的血糖控制受到损害。总之，这些研究将证明PLIN5 S155是PKA介导的脂解所必需的，并建立在大量证据的基础上，证明PLIN5在协调脂质和葡萄糖代谢中发挥关键作用。
Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155 and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis compared with wild-type PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism.
影响因子：
2.5
作者：
Ramos SV;MacPherson RE;Turnbull PC;Bott KN;LeBlanc P;Ward WE;Peters SJ
通讯作者：
Peters SJ