National Institute of Biological Sciences, Beijing 102206, China.
School of Life Sciences, Beijing Normal University, Beijing 100875, China.
Sci Adv. 2022 Oct 28;8(43):eabq1780. doi: 10.1126/sciadv.abq1780. Epub 2022 Oct 26.
Histamine is an important monoamine neurotransmitter that regulates multiple physiological activities in both vertebrates and invertebrates. Clearance and recycling of histamine are critical for sustaining histaminergic transmission. However, unlike other monoamine neurotransmitters, a histamine-specific transporter capable of clearing histamine from the synaptic cleft has not been identified. Here, through an in vitro histamine uptake screening, we identified an epithelial glia-expressing transporter, HisT (tamine ransporter), that specifically transports histamine into cells. HisT misexpression in both pre- and postsynaptic neurons revealed a critical in vivo role for HisT in histamine transport and synaptic transmission. Last, we generated null alleles and demonstrated key physiological roles of HisT in maintaining histamine pools and sustaining visual transmission when the de novo synthesis of histamine synthesis was reduced. Our work identifies the first transporter that specifically recycles histamine and further indicates that the histamine clearance pathway may involve both the uptake-1 and uptake-2 transport systems.
组氨酸是一种重要的单胺神经递质，在脊椎动物和无脊椎动物中调节多种生理活动。组胺的清除和回收对于维持组胺能传递至关重要。然而，与其他单胺神经递质不同，目前尚未鉴定出能够从突触间隙清除组胺的特异性组胺转运体。在这里，我们通过体外组胺摄取筛选，鉴定出一种上皮胶质表达的转运体 HisT（组氨酸转运体），它能将组胺特异性转运到细胞内。HisT 在突触前和突触后神经元中的异位表达揭示了 HisT 在组胺转运和突触传递中的关键体内作用。最后，我们生成了 HisT 的 null 等位基因，并证明了当组胺合成的从头合成减少时，HisT 在维持组胺池和维持视觉传递方面发挥着关键的生理作用。我们的工作鉴定了第一个特异性回收组胺的转运体，并进一步表明组胺清除途径可能涉及摄取-1 和摄取-2 转运系统。
