Functional characteristics and therapeutic potential of SLC41 transporters

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

doi:10.1016/j.jphs.2022.12.003

Functional characteristics and therapeutic potential of SLC41 transporters

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

Authors

Takayuki Nemoto¹, Hideaki Tagashira², Tomo Kita³, Satomi Kita⁴, Takahiro Iwamoto⁵

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Research Institute, Fukuoka University Central Research Organization, Fukuoka, Japan. Electronic address: t.nemoto.dp@fukuoka-u.ac.jp.
² Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
³ Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Research Institute, Fukuoka University Central Research Organization, Fukuoka, Japan.
⁴ Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan; Research Institute, Fukuoka University Central Research Organization, Fukuoka, Japan. Electronic address: satokita@fukuoka-u.ac.jp.
⁵ Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan; Research Institute, Fukuoka University Central Research Organization, Fukuoka, Japan. Electronic address: tiwamoto@fukuoka-u.ac.jp.

PMID: 36707183
DOI: 10.1016/j.jphs.2022.12.003

Abstract

Magnesium (Mg²⁺) 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 Mg²⁺ concentration is tightly regulated by multiple Mg²⁺ transporters and channels. So far, various candidate genes of Mg²⁺ 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 Mg²⁺ transporter/channel MgtE, comprises three isoforms of SLC41A1, SLC41A2, and SLC41A3. Based on recent studies, SLC41A1 is thought to mediate Mg²⁺ influx or Na⁺-dependent Mg²⁺ efflux across the plasma membrane, whereas SLC41A2 and SLC41A3 may mediate Mg²⁺ 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.

Keywords: Mg(2+) transporter; MgtE; Na(+)/Mg(2+) exchanger; SLC41.

Publication types

Review

MeSH terms

Biological Transport
Cell Membrane / metabolism
Humans
Magnesium* / metabolism
Membrane Transport Proteins* / metabolism

Substances

Membrane Transport Proteins
Magnesium