The adiponectin receptor AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 prevent membrane rigidification by exogenous saturated fatty acids.
The adiponectin receptor AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 prevent membrane rigidification by exogenous saturated fatty acids.
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DOI：
10.1371/journal.pgen.1007004
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发表时间：
2017-09
期刊：
影响因子：
4.5
通讯作者：
Pilon M
中科院分区：
文献类型：
--
作者：
Devkota R;Svensk E;Ruiz M;Ståhlman M;Borén J;Pilon M
膳食脂肪酸可以直接并入磷脂。这对细胞膜提出了特殊的挑战，因为它们的组成，因此性质，可能因不同的饮食而有很大的不同。因此，饮食的巨大变化是可以容忍的，这意味着存在监测和调节膜成分的调节机制。本研究表明脂联素受体AdipoR2及其在秀丽隐杆线虫中的同源物PAQR-2对于对抗外源饱和脂肪酸的膜硬化作用至关重要。特别是，我们使用膳食补充剂或突变大肠杆菌作为食物，并直接测量膜流动性和组成，以表明含有高比例饱和脂肪酸和单不饱和脂肪酸的饮食导致paqr-2突变体的膜刚性和致命性。我们还表明，AdipoR2被siRNA敲低的哺乳动物细胞不能阻止棕榈酸的膜固化作用。我们得出结论，PAQR-2和AdipoR2蛋白共享一个进化上保守的功能，即在外源饱和脂肪酸存在下维持膜流动性。我们的细胞及其内部细胞器是由主要由磷脂组成的膜结合在一起的，即含有两个脂肪酸的极性分子，它们附着在一个亲水的头基上。磷脂中脂肪酸的种类对膜的性质有很大的影响：饱和脂肪酸使膜坚硬，而不饱和脂肪酸促进膜的流动性。膳食脂肪可以被吸收到细胞膜中，这一事实对细胞提出了严峻的挑战：如何调节细胞膜的组成来补偿饮食的变化？在本研究中，我们使用不同脂肪组成的细菌突变体作为秀丽隐杆线虫的食物来源，并进行了膜刚性和组成的测定，发现秀丽隐杆线虫的膜蛋白PAQR-2负责检测膳食饱和脂肪酸对膜的硬化作用，并促进脂肪酸去饱和以恢复膜的流动性。我们还研究了PAQR-2的人类同源物，一种叫做AdipoR2的蛋白质，并表明它对防止饱和脂肪酸使膜硬化也是必不可少的。因此，AdipoR2和PAQR-2在细胞中作为进化保守的膜特性调节剂发挥关键作用。
Dietary fatty acids can be incorporated directly into phospholipids. This poses a specific challenge to cellular membranes since their composition, hence properties, could greatly vary with different diets. That vast variations in diets are tolerated therefore implies the existence of regulatory mechanisms that monitor and regulate membrane compositions. Here we show that the adiponectin receptor AdipoR2, and its C. elegans homolog PAQR-2, are essential to counter the membrane rigidifying effects of exogenously provided saturated fatty acids. In particular, we use dietary supplements or mutated E. coli as food, together with direct measurements of membrane fluidity and composition, to show that diets containing a high ratio of saturated to monounsaturated fatty acids cause membrane rigidity and lethality in the paqr-2 mutant. We also show that mammalian cells in which AdipoR2 has been knocked-down by siRNA are unable to prevent the membrane-rigidifying effects of palmitic acid. We conclude that the PAQR-2 and AdipoR2 proteins share an evolutionarily conserved function that maintains membrane fluidity in the presence of exogenous saturated fatty acids. Our cells and their internal organelles are bound by membranes composed primarily of phospholipids, i.e. polar molecules containing two fatty acids attached to a hydrophilic head group. The types of fatty acids in phospholipids greatly influence membrane properties: saturated fatty acids make the membranes rigid while unsaturated fatty acids promote fluidity. The fact that dietary fats can be incorporated into cellular membranes poses a serious challenge to the cells: how to regulate membrane composition to compensate for dietary variations? For the present study we used bacteria mutants with different fat compositions as food sources for the nematode C. elegans, together with assays to determine membrane rigidity and composition, and discovered that the C. elegans membrane protein PAQR-2 is responsible for detecting membrane rigidification by dietary saturated fatty acids and to promote fatty acid desaturation to restore membrane fluidity. We also studied the human homolog of PAQR-2, a protein called AdipoR2, and showed that it too is essential to prevent membrane rigidification by saturated fatty acids. AdipoR2 and PAQR-2 therefore serve a critical function in cells by acting as evolutionarily conserved regulators of membrane properties.
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影响因子：
3.7
作者：
Brooks KK;Liang B;Watts JL
通讯作者：
Watts JL
影响因子：
3.7
作者：
Lindgren A;Levin M;Rodrigo Blomqvist S;Wikström J;Ahnmark A;Mogensen C;Böttcher G;Bohlooly-Y M;Borén J;Gan LM;Lindén D
通讯作者：
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影响因子：
8.1
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Holland WL;Xia JY;Johnson JA;Sun K;Pearson MJ;Sharma AX;Quittner-Strom E;Tippetts TS;Gordillo R;Scherer PE
通讯作者：
Scherer PE
影响因子：
13.5
作者：
Lin, Ling;Ding, Ying;Shen, Huali
通讯作者：
Shen, Huali
影响因子：
4.3
作者：
Bhor, VM;Sivakami, S
通讯作者：
Sivakami, S