SLC41转运蛋白的功能特性及治疗潜力

Functional characteristics and therapeutic potential of SLC41 transporters.

作者信息

Nemoto Takayuki, Tagashira Hideaki, Kita Tomo, Kita Satomi, Iwamoto Takahiro

机构信息

Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Research Institute, Fukuoka University Central Research Organization, Fukuoka, Japan.

Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

出版信息

J Pharmacol Sci. 2023 Feb;151(2):88-92. doi: 10.1016/j.jphs.2022.12.003. Epub 2022 Dec 14.

DOI:10.1016/j.jphs.2022.12.003

PMID:36707183

Abstract

Magnesium (Mg) plays an important role in various cellular functions such as protein synthesis, DNA stability, energy metabolism, enzyme and channel activities, and muscle contractility. Therefore, intracellular Mg concentration is tightly regulated by multiple Mg transporters and channels. So far, various candidate genes of Mg transporters have been identified, and the research on their structure and function is currently in progress. The Solute Carrier 41 (SLC41) family, which is related to the bacterial Mg transporter/channel MgtE, comprises three isoforms of SLC41A1, SLC41A2, and SLC41A3. Based on recent studies, SLC41A1 is thought to mediate Mg influx or Na-dependent Mg efflux across the plasma membrane, whereas SLC41A2 and SLC41A3 may mediate Mg fluxes across either the plasma membrane or organellar membranes. Intriguingly, SLC41A1 variants have been identified in patients with Parkinson's disease (PD) and nephronophthisis-related ciliopathies. Further genetic analyses reveal the association of SLC41A1 polymorphisms with PD risks. This review highlights the recent advances in the understanding of the molecular and functional characteristics of SLC41 family towards its therapeutic and diagnostic applications.

摘要

镁（Mg）在多种细胞功能中发挥着重要作用，如蛋白质合成、DNA稳定性、能量代谢、酶和通道活性以及肌肉收缩性。因此，细胞内镁浓度受到多种镁转运蛋白和通道的严格调控。到目前为止，已经鉴定出多种镁转运蛋白的候选基因，并且对其结构和功能的研究正在进行中。溶质载体41（SLC41）家族与细菌镁转运蛋白/通道MgtE相关，由SLC41A1、SLC41A2和SLC41A3三种亚型组成。基于最近的研究，SLC41A1被认为介导镁通过质膜的内流或钠依赖性镁外流，而SLC41A2和SLC41A3可能介导镁通过质膜或细胞器膜的通量。有趣的是，在帕金森病（PD）和肾单位肾痨相关纤毛病患者中已鉴定出SLC41A1变体。进一步的基因分析揭示了SLC41A1多态性与PD风险的关联。本综述重点介绍了在理解SLC41家族分子和功能特征以用于其治疗和诊断应用方面的最新进展。