Jayaraman Kumaresan, Das Anand K, Luethi Dino, Szöllősi Dániel, Schütz Gerhard J, Reith Maarten E A, Sitte Harald H, Stockner Thomas
Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Institute of Applied Physics, Vienna University of Technology, Vienna, Austria.
J Neurochem. 2021 May;157(4):919-929. doi: 10.1111/jnc.15145. Epub 2020 Aug 28.
Transporters of the solute carrier 6 (SLC6) family mediate the reuptake of neurotransmitters such as dopamine, norepinephrine, serotonin, GABA, and glycine. SLC6 family members are 12 transmembrane helix-spanning proteins that operate using the transmembrane sodium gradient for transport. These transporters assume various quaternary arrangements ranging from monomers to complex stoichiometries with multiple subunits. Dopamine and serotonin transporter oligomerization has been implicated in trafficking of newly formed proteins from the endoplasmic reticulum to the plasma membrane with a pre-fixed assembly. Once at the plasma membrane, oligomers are kept fixed in their quaternary assembly by interaction with phosphoinositides. While it remains unclear how oligomer formation precisely affects physiological transporter function, it has been shown that oligomerization supports the activity of release-type psychostimulants. Most recently, single molecule microscopy experiments unveiled that the stoichiometry differs between individual members of the SLC6 family. The present overview summarizes our understanding of the influence of plasma membrane constituents on transporter oligomerization, describes the known interfaces between protomers and discusses open questions.
溶质载体6（SLC6）家族的转运体介导多巴胺、去甲肾上腺素、5-羟色胺、γ-氨基丁酸和甘氨酸等神经递质的重摄取。SLC6家族成员是具有12个跨膜螺旋的蛋白质，利用跨膜钠梯度进行转运。这些转运体呈现出从单体到具有多个亚基的复杂化学计量比的各种四级结构。多巴胺和5-羟色胺转运体的寡聚化与新形成的蛋白质从内质网到质膜的固定装配转运有关。一旦到达质膜，寡聚体通过与磷酸肌醇相互作用而保持其四级装配固定。虽然尚不清楚寡聚体形成如何精确影响生理转运体功能，但已表明寡聚化支持释放型精神兴奋剂的活性。最近，单分子显微镜实验揭示，SLC6家族各成员之间的化学计量比不同。本综述总结了我们对质膜成分对转运体寡聚化影响的理解，描述了原体之间已知的界面，并讨论了未解决的问题。
