PAQR-2 regulates fatty acid desaturation during cold adaptation in C. elegans.

PAQR-2 regulates fatty acid desaturation during cold adaptation in C. elegans.
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DOI:
10.1371/journal.pgen.1003801
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发表时间:
2013
期刊:
影响因子:
4.5
通讯作者:
Pilon M
Pilon M
中科院分区:
生物学2区
文献类型:
--
作者:
Svensk E;Ståhlman M;Andersson CH;Johansson M;Borén J;Pilon M

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线虫 PAQR-2 与哺乳动物中的胰岛素增敏脂联素受体同源,对于适应 15°C 的生长至关重要,这是该生物体较低但通常可接受的温度。通过筛选新型 paqr-2 抑制剂,我们鉴定了参与磷脂酰胆碱合成(cept-1、pcyt-1 和 sams-1)和脂肪酸代谢(ech-7、hacd-1、mdt-15、nhr-49 和 sbp-1)的基因突变。然后,我们展示了遗传证据,表明 paqr-2、磷脂酰胆碱、sbp-1 和 Δ9-去饱和酶形成冷适应途径,调节在低温下保持膜流动性所需的不饱和脂肪酸的增加。该模型得到以下观察结果的支持:paqr-2 抑制剂使饱和脂肪酸水平正常化,并且增加膜流动性的低浓度去垢剂可以拯救 paqr-2 突变体。当环境温度降低时,昆虫、鱼或蠕虫等冷血生物必须做出生理调整。一项重要的适应性措施是增加由脂肪分子组成的细胞膜的流动性,细胞膜在低温下会像黄油一样变硬。在我们的研究中,我们鉴定了受 PAQR-2 调节的基因,PAQR-2 是一种膜蛋白,我们证明 PAQR-2 对于在线虫冷适应过程中调节膜流动性至关重要。有趣的是,受PAQR-2影响的基因都与脂肪酸代谢有关。我们推测 PAQR-2 的人类同源物(脂联素激素受体)可能具有类似的功能。
C. elegans PAQR-2 is homologous to the insulin-sensitizing adiponectin receptors in mammals, and essential for adaptation to growth at 15°C, a low but usually acceptable temperature for this organism. By screening for novel paqr-2 suppressors, we identified mutations in genes involved in phosphatidylcholine synthesis (cept-1, pcyt-1 and sams-1) and fatty acid metabolism (ech-7, hacd-1, mdt-15, nhr-49 and sbp-1). We then show genetic evidence that paqr-2, phosphatidylcholines, sbp-1 and Δ9-desaturases form a cold adaptation pathway that regulates the increase in unsaturated fatty acids necessary to retain membrane fluidity at low temperatures. This model is supported by the observations that the paqr-2 suppressors normalize the levels of saturated fatty acids, and that low concentrations of detergents that increase membrane fluidity can rescue the paqr-2 mutant. Cold-blooded organisms such as insects, fish or worms must make physiological adjustments when the temperature in their environment decreases. One essential adaptive measure is to increase the fluidity of the cellular membranes that are made of fatty molecules and would tend to harden at low temperatures, just as butter would. In our study we identify genes that are regulated by PAQR-2, a membrane protein that we show to be essential for adjusting the membrane fluidity during cold adaptation in the nematode C. elegans. Interestingly, the genes influenced by PAQR-2 are all involved in fatty acid metabolism. We speculate that the human homologs of PAQR-2, which are receptors for the hormone adiponectin, may have similar functions.
秀丽隐杆线虫中不饱和脂肪酸组成的遗传调节。
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