Abstract:
Transporters of the monoamine transporter (MAT) family regulate the uptake of important neurotransmitters like dopamine, serotonin, and norepinephrine. The MAT family functions using the electrochemical gradient of ions across the membrane and comprises three transporters, dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET). MAT transporters have been observed to exist in monomeric states to higher-order oligomeric states. Structural features, allosteric modulation, and lipid environment regulate the oligomerization of MAT transporters. NET and SERT oligomerization are regulated by levels of PIP2 present in the membrane. The kink present in TM12 in the MAT family is crucial for dimer interface formation. Allosteric modulation in the dimer interface hinders dimer formation. Oligomerization also influences the transporters\' function, trafficking, and regulation. This chapter will focus on recent studies on monoamine transporters and discuss the factors affecting their oligomerization and its impact on their function.
摘要:
单胺转运蛋白(MAT)家族的转运蛋白调节多巴胺等重要神经递质的摄取,血清素,和去甲肾上腺素.MAT家族使用离子跨膜的电化学梯度起作用,包括三个转运蛋白,多巴胺转运蛋白(DAT),血清素转运体(SERT),和去甲肾上腺素转运蛋白(NET)。已观察到MAT转运蛋白以单体状态存在至高阶寡聚状态。结构特征,变构调制,和脂质环境调节MAT转运蛋白的寡聚化。NET和SERT寡聚化受膜中存在的PIP2水平的调节。MAT家族中TM12中存在的扭结对于二聚体界面形成至关重要。二聚体界面中的变构调制阻碍了二聚体的形成。低聚也会影响转运蛋白的功能,贩运,和监管。本章将重点介绍最近对单胺转运体的研究,并讨论影响其寡聚化的因素及其对其功能的影响。