Overview of mammalian zinc transporters

Abstract

In recent years, a number of mammalian zinc transporters have been identified, and candidate genes are rapidly growing. These transporters are classified into two families: ZIP (ZRT, IRT-like protein) and CDF (cation diffusion facilitator). ZIP members facilitate zinc influx into the cytosol, while CDF members facilitate its efflux from the cytosol. Molecular characterization of the transporters has brought about major advances in our understanding of their physiological functions. Zinc metabolism is regulated primarily through zinc-dependent control of transcription, translation, and intracellular trafficking of transporters. Analyses of mice whose zinc transporter genes have been genetically disrupted and of the naturally occurring mutant mice with symptoms related to abnormal zinc metabolism have provided compelling evidence that some zinc transporters play critical roles in zinc homeostasis. In this review, we review the literature of mammalian zinc transporters with emphasis on very recent findings and elicit integrative knowledge of zinc homeostasis.

Demonstration and Characterization of the Heterodimerization of ZnT5 and ZnT6 in the Early Secretory Pathway

“…These results suggest the Ser-rich loop is not essential for zinc transport by hZnT5/ hZnT6 heterodimers but is required if optimum activity is to be achieved. Interestingly, several human cell types 3 and cell lines 4 express a splice variant of hZnT6 mRNA lacking exon 9, which encodes most of this Ser-rich loop. It is plausible that hZnT6 and its vertebrate orthologues function as modulators of zinc transport activity by ZnT5/ZnT6 heterodimers via this Ser-rich loop.…”

“…Zinc transporter (SLC30A) proteins, also known as CDF/ ZnTs, 2 are responsible for the efflux of cytosolic zinc from cells and the mobilization of zinc into intracellular organelles to remove the excess zinc and to ensure a supply of zinc to zincbinding proteins (1)(2)(3)(4)(5)(6)(7)(8). Recently, more data about the biochemical properties of these transporter molecules have been published, including their substrate specificity, structural conformation, metal transport mechanisms, and cellular or physiological functions (1, 5, 8 -13).…”

Differences in the humoral autoreactivity to zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients

“…All subjects were informed the purpose of the study, and their consent for study participation was obtained. Protocols were approved by the ethics committee of Nagasaki 5 University and the Japan Diabetes Society. Sera were stored at −20°C until use.…”

“…Recently, the cation efflux transporter zinc transporter 8 (ZnT8) has been identified as a novel target autoantigen in patients with type 1 diabetes [4]. Zinc transporters are multipass transmembrane proteins that function in the transport of zinc out of the cytoplasm or into vesicles [5]. ZnT8 is specifically expressed in the pancreatic β-cells and plays a major role in insulin maturation [4,6].…”

Restraint stress up-regulates expression of zinc transporter Zip14 mRNA in mouse liver

“…Zinc homeostasis is mostly regulated by zinc transporters (Eide 2006). Known eukaryotic zinc transporters are largely classified into two families, the ZRT/IRT-like Protein (ZIP) and Cation Diffusion Facilitator (CDF) families, which are designated as ''SLC39'', and ''SLC30'', respectively (Cousins et al 2006;Kambe et al 2004). ZIP members facilitate zinc influx into the cytosol, while CDF members facilitate its efflux from the cytosol.…”