The Functional Activity of the Human Serotonin 5-HT1A Receptor Is Controlled by Lipid Bilayer Composition
The Functional Activity of the Human Serotonin 5-HT1A Receptor Is Controlled by Lipid Bilayer Composition
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DOI：
10.1016/j.bpj.2016.04.042
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发表时间：
2016-06-07
影响因子：
3.4
通讯作者：
Malmstadt, Noah
中科院分区：
文献类型：
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作者：
Gutierrez, M. Gertrude;Mansfield, Kylee S.;Malmstadt, Noah
虽然细胞质膜脂双层的性质被广泛理解为影响膜蛋白的组成，这些相互作用的细节知之甚少。这对于G蛋白偶联受体（GPCR）的大家族尤其如此。在这里，我们研究了人类血清素5-HT 1A受体，一个GPCR是中央神经元功能的脂质依赖性。我们将该蛋白质整合到组成受控的合成双层中，并与荧光报告系统一起检测GPCR催化的G蛋白激活，以测量受体催化的寡核苷酸交换。我们的研究结果表明，增加膜秩序诱导的甾醇和鞘磷脂增加受体催化的寡核苷酸交换。增加膜弹性曲率应力也增加这种交换。这些结果揭示了5-HT 1A受体对质膜性质的广泛依赖性，表明膜脂质组成是一个生化控制参数，并强调了与衰老，饮食或疾病相关的组成变化可能影响细胞信号传导功能的可能性。
Although the properties of the cell plasma membrane lipid bilayer are broadly understood to affect integral membrane proteins, details of these interactions are poorly understood. This is particularly the case for the large family of G protein-coupled receptors (GPCRs). Here, we examine the lipid dependence of the human serotonin 5-HT1A receptor, a GPCR that is central to neuronal function. We incorporate the protein in synthetic bilayers of controlled composition together with a fluorescent reporting system that detects GPCR-catalyzed activation of G protein to measure receptor-catalyzed oligonucleotide exchange. Our results show that increased membrane order induced by sterols and sphingomyelin increases receptor-catalyzed oligonucleotide exchange. Increasing membrane elastic curvature stress also increases this exchange. These results reveal the broad dependence that the 5-HT1A receptor has on plasma membrane properties, demonstrating that membrane lipid composition is a biochemical control parameter and highlighting the possibility that compositional changes related to aging, diet, or disease could impact cell signaling functions.