Institute of Pharmacology and the Gaston H. Glock Research Laboratories for Exploratory Drug Development, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
J Biol Chem. 2023 Apr;299(4):104618. doi: 10.1016/j.jbc.2023.104618. Epub 2023 Mar 17.
The level of dopamine transporters (DATs) in the neuronal plasma membrane shapes learning and motor coordination in mice. Mechanisms underlying the regulated internalization of DAT and its return to the cell surface have been intensively studied in heterologous cells and in neuronal cell bodies. However, whether this cycling also happens in synaptic boutons, or axon terminals, thought to be the major functional site for DAT expression, was an open question that Kearney and colleagues recently addressed in the JBC. They showed that DAT cycling in the presynaptic specialization of dopaminergic neurons is subject to control by a cell-autonomous loop comprising dopamine autoreceptors and metabotropic glutamate receptors. These results should inform future studies in neural development and motor learning.
神经元质膜中的多巴胺转运体 (DAT) 水平影响着小鼠的学习和运动协调能力。DAT 的调节内吞作用及其返回细胞表面的机制已在异源细胞和神经元胞体中得到了深入研究。然而，这种循环是否也发生在突触小泡或轴突末梢中，这些部位被认为是 DAT 表达的主要功能部位，这是一个悬而未决的问题，Kearney 及其同事最近在 JBC 上进行了探讨。他们表明，多巴胺能神经元突触前特化中的 DAT 循环受到包含多巴胺自身受体和代谢型谷氨酸受体的细胞自主循环的控制。这些结果将为神经发育和运动学习的未来研究提供信息。
