National Institute of Biological Sciences, Beijing, China.
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
Elife. 2022 Mar 1;11:e75821. doi: 10.7554/eLife.75821.
Neurotransmitters are generated by de novo synthesis and are essential for sustained, high-frequency synaptic transmission. Histamine, a monoamine neurotransmitter, is synthesized through decarboxylation of histidine by histidine decarboxylase (Hdc). However, little is known about how histidine is presented to Hdc as a precursor. Here, we identified a specific histidine transporter, TADR (torn and diminished rhabdomeres), which is required for visual transmission in . Both TADR and Hdc localized to neuronal terminals, and mutations in reduced levels of histamine, thus disrupting visual synaptic transmission and phototaxis behavior. These results demonstrate that a specific amino acid transporter provides precursors for monoamine neurotransmitters, providing the first genetic evidence that a histidine amino acid transporter plays a critical role in synaptic transmission. These results suggest that TADR-dependent local de novo synthesis of histamine is required for synaptic transmission.
神经递质是通过从头合成产生的，对持续的高频突触传递至关重要。组氨酸是一种单胺类神经递质，通过组氨酸脱羧酶（Hdc）将组氨酸脱羧生成。然而，人们对组氨酸作为前体如何被递呈给 Hdc 知之甚少。在这里，我们鉴定出一种特定的组氨酸转运蛋白 TADR（撕裂和减少的纤毛），它是 在视觉传递中必需的。TADR 和 Hdc 都定位于神经元末梢，而 中的突变降低了组氨酸的水平，从而破坏了视觉突触传递和趋光行为。这些结果表明，一种特定的氨基酸转运蛋白为单胺类神经递质提供前体，这为氨基酸转运蛋白在突触传递中发挥关键作用提供了第一个遗传证据。这些结果表明，TADR 依赖性局部从头合成组氨酸是突触传递所必需的。
