金属转运蛋白SLC39A8的功能及作用机制研究进展  

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

作　　者：彭云 李洋[1] 石亚菲 任怡静 王福俤 PENG Yun;LI Yang;SHI Ya-Fei;REN Yi-Jing;WANG Fu-Di(Precision Nutrition Innovation Institute,School of Public Health,Zhengzhou University,Zhengzhou 450001,China;School of Public Health,Zhejiang University School of Medicine,Hangzhou 310058,China)

机构地区：[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

出　　处：《生命科学》2021年第11期1318-1331,共14页Chinese Bulletin of Life Sciences

基　　金：国家重点研发计划(2018YFA0507800);国家自然科学基金项目(31930057,31530034)。

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。SLC39 A8,also known as ZIP8,is an important member of solute carrier family 39(SLC39).Recently,the functional mechanism of SLC39 A8 has made great progress.It has been found that SLC39 A8 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 SLC39 A8 caused severe manganese deficiency in the body,suggesting that manganese is the main functional substrate of SCL39 A8.The expression of SLC39 A8 can be detected in many tissues and organs,among which SLC39 A8 expression is abundant in the lung,pancreas and placenta.Studies have reported that SLC39 A8 plays key roles in immune function,insulin secretion,skeletal disease and liver disease.The global knockout of Slc39 a8 can lead to embryo death in mice.Multiple polymorphic sites of SLC39 A8 were found in genome-wide association studies,among which rs13107325(p.Ala391 Thr)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 SLC39 A8 on function and molecular mechanism,and future research directions are also discussed and prospected.

关 键 词：SLC39A8 ZIP8 锰代谢 锌代谢 铁代谢 转运蛋白 人类疾病 

分 类 号：Q952.5[生物学—动物学]