《生命科学》 2020, 32(9): 890-902

金属转运蛋白SLC39A14的生理功能及作用机制研究进展

周梦瑶¹ , 王　浩¹ , 尚艳娜¹ , 李　洋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：

溶质载体家族39 (solute carrier family 39, SLC39; Zrt- and Irt-like proteins, ZIPs)作为金属离子转运蛋白家族共包括14个成员，均具有8个跨膜结构域。近年来，国内外研究者围绕SLC39A14 (又称ZIP14)的离子转运及生理功能开展了深入研究，提示SLC39A14具有转运Mn2+、Fe2+或Zn2+等二价金属离子的功能，并通过转运Fe2+而参与细胞铁死亡的发生。携带SLC39A14基因纯合突变的患者表现为锰离子蓄积及年轻型帕金森样体征。此外，有研究报道SLC39A14在肝脏疾病、胰岛素代谢、脂代谢及肌肉疾病中发挥关键作用，为丰富微量元素代谢调控网络及疾病防控提供了重要理论依据。然而，Slc39a14全身敲除与组织特异性敲除小鼠之间的表型不尽相同，因此其在不同组织中的金属离子转运功能及机制尚待深入研究。该文系统综述了SLC39A14在金属离子转运、代谢紊乱疾病和分子调控机制等方面的研究进展，并就未来研究方向进行了展望和讨论。

通讯作者：王福俤 , Email:fwang@zju.edu.cn

Molecular mechanisms and physiological functions of metal transporter SLC39A14

ZHOU Meng-Yao¹ , WANG Hao¹ , SHANG Yan-Na¹ , LI Yang¹ , 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:

The solute carrier family 39 (SLC39) consists of 14 members that function as metal importer. This protein family has 8 transmembrane domains. Recently, physiological functions of SLC39A14 (also known as ZIP14) have drawn a lot of attention. It is reported that SLC39A14 could transport divalent metal ions such as Fe2+, Mn2+ and Zn2+. Slc39a14 participates in the active transportation of Fe2+ into cells, which triggers ferroptosis. Patients with autosomal recessive mutations of SLC39A14 presented severe accumulation of manganese and developed early-onset rapidly-progressive parkinsonism-dystonia and neurodegeneration. Emerging studies reported that SLC39A14 might play important roles in liver disease, insulin resistance, lipid metabolism and muscle dysfunction. Using global and tissue-specific Slc39a14 knockout mice, several studies have shown that Slc39a14 could transport multiple metals in mice. However, tissue specific role of Slc39a14 remains to be elucidated. This review article summarizes recent progress of the transporter function of SLC39A14 and its potential underlying mechanisms in metabolic disorders and related diseases, and also discusses our perspectives about the future research direction.

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