《生命科学》 2021, 33(11): 1318-1331

金属转运蛋白SLC39A8的功能及作用机制研究进展

彭　云¹ , 李　洋¹ , 石亚菲¹ , 任怡静¹ , 王福俤^1,2,*

¹郑州大学公共卫生学院精准营养创新中心，郑州 450001 ²浙江大学医学院公共卫生学院，杭州 310058

摘　要：

SLC39A8，又称为ZIP8，是溶质载体家族39 (solute carrier family 39, SLC39; Zrt- and Irt-like proteins, ZIPs) 重要成员。近年来，国内外研究在SLC39A8 的离子转运及功能机制方面取得重大进展。研究发现，SLC39A8 不仅能转运锰、锌、铁和硒等必需微量元素，还可转运重金属镉。人类遗传学及系列转基因小鼠模型表明，SLC39A8 突变或缺失引发机体严重锰缺乏，提示锰是SCL39A8 的主要功能底物。SLC39A8 在机体众多组织器官表达，其中肺、胰腺和胎盘表达量相对较高。有研究报道SLC39A8 在免疫功能、胰岛素分泌、骨骼疾病以及肝脏疾病等中发挥重要作用，其中Slc39a8 全身敲除可致小鼠胚胎致死。全基因组关联分析发现了SLC39A8 的多个多态性位点，其中rs13107325 (p.Ala391Thr) 位点研究较多，该位点突变与血锰水平降低、青少年特发性脊柱侧凸、精神分裂症、克罗恩病和肠道菌群改变以及心脑血管代谢性疾病等有关。该文就SLC39A8 的功能和作用机制研究进展作系统性综述，并对未来研究方向进行讨论和展望。

通讯作者：王福俤 , Email:fwang@zju.edu.cn

Research progress in physiological functions and molecular mechanisms of metal transporter SLC39A8

PENG Yun¹ , LI Yang¹ , SHI Ya-Fei¹ , REN Yi-Jing¹ , WANG Fu-Di^1,2,*

¹Precision Nutrition Innovation Institute, School of Public Health, Zhengzhou University, Zhengzhou 450001, China ²School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China

Abstract:

SLC39A8, also known as ZIP8, is an important member of solute carrier family 39 (SLC39). Recently, the functional mechanism of SLC39A8 has made great progress. It has been found that SLC39A8 can transport multiple essential trace elements, such as manganese, zinc, iron, and selenium, as well as heavy metal cadmium. Human genetics and a series of transgenic mouse models showed that the mutation or deletion of SLC39A8 caused severe manganese deficiency in the body, suggesting that manganese is the main functional substrate of SCL39A8. The expression of SLC39A8 can be detected in many tissues and organs, among which SLC39A8 expression is abundant in the lung, pancreas and placenta. Studies have reported that SLC39A8 plays key roles in immune function, insulin secretion, skeletal disease and liver disease. The global knockout of Slc39a8 can lead to embryo death in mice. Multiple polymorphic sites of SLC39A8 were found in genome-wide association studies, among which rs13107325 (p.Ala391Thr) has been studied more widely. The mutation of this site was associated with decreased blood manganese level, adolescent idiopathic scoliosis, schizophrenia, Crohn's disease, the change of gut microbiome composition and cardiovascular and cerebrovascular metabolic diseases. This review systematically summarizes the research progress of SLC39A8 on function and molecular mechanism, and future research directions are also discussed and prospected.

Communication Author：WANG Fu-Di , Email:fwang@zju.edu.cn