《生命科学》 2018, 30(6): 603-614

锰离子转运蛋白的发现及功能机制研究进展

黄　鑫1#，李玲玲1#，王君豪1#，闵军霞2*，王福俤1，3*

(1 郑州大学公共卫生学院精准营养创新中心，郑州 450001；2 浙江大学医学院转化
    医学研究院，杭州 300085；3 浙江大学医学院公共卫生学院，杭州 300085)

摘　要：摘　要：锰是维持人体健康的必需微量元素。锰缺乏或过量均可促发系列重大疾病发生。机体或细胞锰离子的稳态维持受多个锰离子转运蛋白的调控。近年，三个关键的锰离子转运蛋白SLC39A8、SLC39A14 和SLC30A10 相继被发现，这些基因突变可直接导致锰代谢异常所致的人类遗传病；同时，相关基因敲除或转基因模式动物模型不仅能够模拟人类锰代谢异常的症状，而且可深入研究这些锰离子转运蛋白在器官和细胞内的功能及其分子调控机制，从而开启了锰稳态调控研究的崭新征程。此外，有研究提示二价金属转运蛋白1 (DMT1)、膜铁转运蛋白(FPN)、转铁蛋白/ 转铁蛋白受体系统(TF/TfR)、TMEM165、分泌型Ca2+通道1 (SPCA1) 及ATP13A2 等膜蛋白也可能参与细胞锰离子转运，使得锰离子的稳态调控变得更为复杂。现就锰转运蛋白的发现及功能机制研究的国内外进展作系统性综述，为后续研究提供新思路。

Functional discoveries and mechanistic studies of manganese transporters

HUANG Xin1#， LI Ling-Ling1#， WANG Jun-Hao1#， MIN Jun-Xia2*， WANG Fu-Di1，3*

(1 Precision Nutrition Innovation Institute， School of Public Health， Zhengzhou University， Zhengzhou 450001， China; 2 Institute of Translational Medicine， Zhejiang University School of Medicine， Hangzhou 310058， China; 3 School of Public Health， Zhejiang University School of Medicine， Hangzhou 310058， China)

Abstract: Abstract: Manganese (Mn) is an essential trace element for maintaining human health. Its homeostasis is regulated by multiple Mn transporters at cellular levels. Both Mn excess and deficiency could cause severe pathological conditions. To date， three key Mn transporters， including SLC39A8， SLC39A14 and SLC30A10， have been identified and functionally characterized as causal mutations in Mn-related human inherited diseases and in several model organisms. In addition， it has been reported that DMT1， Ferroportin， Tf/TfR， TMEM165， SPCA1 and ATP13A2 might be involved in transporting Mn， which makes Mn metabolism a complex process. In this review article， we summarized the current progress of functional discoveries of these Mn transporters and their proposed molecular mechanisms to pave the way for better understanding and management of Mn-related conditions.