Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in Caenorhabditis elegans
Neuronal control of lipid metabolism by STR-2 G protein-coupled receptor promotes longevity in Caenorhabditis elegans
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DOI：
10.1111/acel.13160
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发表时间：
2020-05-20
期刊：
影响因子：
7.8
通讯作者：
Singh, Varsha
中科院分区：
文献类型：
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作者：
Dixit, Anubhuti;Sandhu, Anjali;Singh, Varsha
G蛋白偶联受体（GPCR）编码基因家族占秀丽隐杆线虫基因组基因的6%以上。 GPCR 控制行为、先天免疫、趋化性和食物搜索行为。在这里，我们发现线虫的寿命受到化学感应 GPCR STR-2 的调节，该化学感应 GPCR STR-2 在 AWC 和 ASI 两栖类感觉神经元中表达。标准大肠杆菌 OP50 饮食在 20 摄氏度及以上的温度下需要 STR-2 功能。在这些条件下，这种神经元受体还控制健康跨度参数和肠道内的脂滴 (LD) 稳态。我们发现 STR-2 调节 delta-9 去饱和酶、fat-5、fat-6 和 fat-7 以及二酰基甘油酰基转移酶 dgat-2 的表达。拯救 AWC 和 ASI 或单独的 ASI 感觉神经元中的 STR-2 功能，可恢复 fat-5、dgat-2 的表达并恢复 LD 储存和寿命。用低浓度葡萄糖将 GPCR 突变动物的储存脂肪水平恢复至野生型水平，可以挽救其寿命表型。总之，我们表明神经元 STR-2 GPCR 有助于控制线虫的中性脂质水平和寿命。
The G protein-coupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. elegans longevity is regulated by a chemosensory GPCR STR-2, expressed in AWC and ASI amphid sensory neurons. STR-2 function is required at temperatures of 20 degrees C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR-2 regulates expression of delta-9 desaturases, fat-5, fat-6 and fat-7, and of diacylglycerol acyltransferase dgat-2. Rescue of the STR-2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of fat-5, dgat-2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wild-type levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR-2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans.