Baudry Anne, Pietri Mathea, Launay Jean-Marie, Kellermann Odile, Schneider Benoit
INSERM UMR-S 1124, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1124, Paris, France.
Front Neurosci. 2019 Feb 12;13:91. doi: 10.3389/fnins.2019.00091. eCollection 2019.
Serotonin transporter, SERT ( for solute carrier family 6, member A4), is a twelve transmembrane domain (TMDs) protein that assumes the uptake of serotonin (5-HT) through dissipation of the Na gradient established by the electrogenic pump Na/K ATPase. Abnormalities in 5-HT level and signaling have been associated with various disorders of the central nervous system (CNS) such as depression, obsessive-compulsive disorder, anxiety disorders, and autism spectrum disorder. Since the 50s, SERT has raised a lot of interest as being the target of a class of antidepressants, the Serotonin Selective Reuptake Inhibitors (SSRIs), used in clinics to combat depressive states. Because of the refractoriness of two-third of patients to SSRI treatment, a better understanding of the mechanisms regulating SERT functions is of priority. Here, we review how genetic and epigenetic regulations, post-translational modifications of SERT, and specific interactions between SERT and a set of diverse partners influence SERT expression, trafficking to and away from the plasma membrane and activity, in connection with the neuronal adaptive cell response to SSRI antidepressants.
血清素转运体，即SERT（溶质载体家族6成员A4），是一种具有十二个跨膜结构域（TMDs）的蛋白质，它通过消耗由电生泵钠钾ATP酶建立的钠梯度来摄取血清素（5 - HT）。5 - HT水平和信号传导异常与多种中枢神经系统（CNS）疾病相关，如抑郁症、强迫症、焦虑症和自闭症谱系障碍。自20世纪50年代以来，SERT作为一类抗抑郁药——血清素选择性再摄取抑制剂（SSRIs）的作用靶点，引发了广泛关注，这类药物在临床上用于对抗抑郁状态。由于三分之二的患者对SSRI治疗存在耐药性，因此深入了解调节SERT功能的机制成为当务之急。在此，我们综述了遗传和表观遗传调控、SERT的翻译后修饰，以及SERT与一系列不同伙伴之间的特定相互作用如何影响SERT的表达、向质膜转运及从质膜转运离开和活性，这与神经元对SSRI抗抑郁药的适应性细胞反应相关。
