Lipid microdomains ("rafts") are dynamic, nanoscale regions of the plasma membrane enriched in cholesterol and glycosphingolipids, that possess distinctive physicochemical properties including higher order than the surrounding membrane. Lipid microdomain integrity is thought to affect neurotransmitter signaling by regulating membrane-bound protein signaling. Among the proteins potentially affected are monoaminergic receptors and transporters. As dysfunction of monoaminergic neurotransmission is implicated in major depressive disorder and other neuropsychiatric conditions, interactions with lipid microdomains may be of clinical importance. This systematic review evaluates what is known about the molecular relationships of monoamine transporter and receptor regulation to lipid microdomains. The PubMed/MeSH database was searched for original studies published in English through August 2017 concerning relationships between lipid microdomains and serotonin, dopamine and norepinephrine transporters and receptors. Fifty-seven publications were identified and assessed. Strong evidence implicates lipid microdomains in the regulation of serotonin and norepinephrine transporters; serotonin 1A, 2A, 3A, and 7A receptors; and dopamine D1 and β2 adrenergic receptors. Results were conflicting or more complex regarding lipid microdomain associations with the dopamine transporter, D2, D3, and D5 receptors; and negative with respect to β1 adrenergic receptors. Indirect evidence suggests that antidepressants, lipid-lowering drugs, and polyunsaturated fatty acids may exert effects on depression and suicide by altering the lipid milieu, thereby affecting monoaminergic transporter and receptor signaling. The lipid composition of membrane subdomains is involved in localization and trafficking of specific monoaminergic receptors and transporters. Elucidating precise mechanisms whereby lipid microdomains modulate monoamine neurotransmission in clinical contexts can have critical implications for pharmacotherapeutic targeting.

中文翻译：

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脂质微区对单胺转运蛋白和受体的调节：对抑郁症的影响。

脂质微域（“筏”）是质膜的动态纳米级区域，富含胆固醇和鞘糖脂，具有独特的理化特性，包括比周围膜更高的阶数。脂质微结构域完整性被认为通过调节膜结合蛋白信号传导来影响神经递质信号传导。可能受影响的蛋白质包括单胺能受体和转运蛋白。由于单胺能神经传递功能障碍与重度抑郁症和其他神经精神疾病有关，因此与脂质微区的相互作用可能具有临床重要性。本系统综述评估了单胺转运蛋白和受体调节与脂质微结构域的分子关系的已知情况。在 PubMed/MeSH 数据库中检索了截至 2017 年 8 月以英文发表的关于脂质微结构域与血清素、多巴胺和去甲肾上腺素转运蛋白和受体之间关系的原始研究。确定并评估了 57 份出版物。强有力的证据表明脂质微结构域参与血清素和去甲肾上腺素转运蛋白的调节；血清素 1A、2A、3A 和 7A 受体；以及多巴胺 D1 和 β2 肾上腺素能受体。关于脂质微结构域与多巴胺转运蛋白、D2、D3 和 D5 受体的关联，结果相互矛盾或更复杂；β1 肾上腺素能受体呈阴性。间接证据表明，抗抑郁药、降脂药和多不饱和脂肪酸可能通过改变脂质环境，从而影响单胺能转运蛋白和受体信号传导，对抑郁和自杀产生影响。膜亚结构域的脂质组成参与特定单胺能受体和转运蛋白的定位和运输。阐明脂质微结构域在临床环境中调节单胺神经传递的精确机制可能对药物治疗靶向具有重要意义。