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Title: Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels
Authors: Nishito, Yukina  KAKEN_id
Kambe, Taiho  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-9757-063X (unconfirmed)
Author's alias: 西藤, 有希奈
神戸, 大朋
Keywords: zinc
transporter
plasma membrane
endocytosis
glycosylation
metal homeostasis
degradation
metallothionein
ZNT
Issue Date: 25-Oct-2019
Publisher: American Society for Biochemistry & Molecular Biology (ASBMB)
Journal title: Journal of Biological Chemistry
Volume: 294
Issue: 43
Start page: 15686
End page: 15697
Abstract: Zinc transporter 1 (ZNT1) is the only zinc transporter predominantly located on the plasma membrane, where it plays a pivotal role exporting cytosolic zinc to the extracellular space. Numerous studies have focused on the physiological and pathological functions of ZNT1. However, its biochemical features remain poorly understood. Here, we investigated the regulation of ZNT1 expression in human and vertebrate cells, and found that ZNT1 expression is posttranslationally regulated by cellular zinc status. We observed that under zinc-sufficient conditions, ZNT1 accumulates on the plasma membrane, consistent with its zinc efflux function. In contrast, under zinc-deficient conditions, ZNT1 molecules on the plasma membrane were endocytosed and degraded through both the proteasomal and lysosomal pathways. Zinc-responsive ZNT1 expression corresponded with that of metallothionein, supporting the idea that ZNT1 and metallothionein cooperatively regulate cellular zinc homeostasis. ZNT1 is N-glycosylated on Asn299 in the extracellular loop between transmembrane domains V and VI, and this appears to be involved in the regulation of ZNT1 stability, as nonglycosylated ZNT1 is more stable. However, this posttranslational modification had no effect on ZNT1's ability to confer cellular resistance against high zinc levels or its subcellular localization. Our results provide molecular insights into ZNT1-mediated regulation of cellular zinc homeostasis, and indicate that the control of cellular and systemic zinc homeostasis via dynamic regulation of ZNT1 expression is more sophisticated than previously thought.
Rights: This research was originally published in the Journal of Biological Chemistry. Nishito Yukina and Kambe Taiho. Zinc transporter 1 (ZNT1) expression on the cell surface is elaborately controlled by cellular zinc levels. J. Biol. Chem. 2019; 294: 15686-15697. © 2019 Nishito and Kambe.
The full-text file will be made open to the public on 25 October 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
URI: http://hdl.handle.net/2433/244791
DOI(Published Version): 10.1074/jbc.RA119.010227
PubMed ID: 31471319
Appears in Collections:Journal Articles

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