Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis

Abstract

Zinc (Zn) is an essential trace mineral that regulates the expression and activation of biological molecules such as transcription factors, enzymes, adapters, channels, and growth factors, along with their receptors. Zn deficiency or excessive Zn absorption disrupts Zn homeostasis and affects growth, morphogenesis, and immune response, as well as neurosensory and endocrine functions. Zn levels must be adjusted properly to maintain the cellular processes and biological responses necessary for life. Zn transporters regulate Zn levels by controlling Zn influx and efflux between extracellular and intracellular compartments, thus, modulating the Zn concentration and distribution. Although the physiological functions of the Zn transporters remain to be clarified, there is growing evidence that Zn transporters are related to human diseases, and that Zn transporter-mediated Zn ion acts as a signaling factor, called "Zinc signal". Here we describe critical roles of Zn transporters in the body and their contribution at the molecular, biochemical, and genetic levels, and review recently reported disease-related mutations in the Zn transporter genes.

Novel Nonsense Mutation in SLC39A13 Initially Presenting as Myopathy: Case Report and Review of the Literature

“…4 ) [Bin et al, 2011]. ZIP13 belongs to one of 2 main groups of zinc transporters (ZnT/SLC30A and ZIP/ SLC39A) confirmed to participate in maintaining cellular zinc homoeostasis [Jeong and Eide, 2013;Kambe et al, 2015a;Kimura and Kambe, 2016;Hara et al, 2017]. In contrast to Zn transporters, ZIP family members operate as influx transporters moving zinc from extracellular fluids or intracellular organelles into the cytosol.…”

“…In contrast to Zn transporters, ZIP family members operate as influx transporters moving zinc from extracellular fluids or intracellular organelles into the cytosol. Zn transporters have also been proven to participate in intracellular zinc-related signaling [Hirano et al, 2008;Fukada et al, 2013;Hara et al, 2017]. Imbalances in cellular zinc distribution lead to a diversity of symptoms (e.g., toxicity, copper or zinc deficiency syndromes) presenting with mild to severe or even life-threatening forms [Bin et al, 2011;Hara et al, 2017].…”

Emerging role of zinc homeostasis by zinc transporter ZIP7 in intestinal homeostatic self-renewal

“…Zinc is an essential trace element required for maintaining the homeostasis of our body [1] . When the level of zinc is decreased in the body, various symptoms associated with deficiency of zinc, such as growth retardation, immunodeficiency, and disordered-homeostasis of intestinal epithelium, are observed [2] .…”

Co-localization of zinc transporter 3 (ZnT3) with sensory neuromediators and/or neuromodulators in the enteric nervous system of the porcine esophagus

“…This metal, as a key component of many proteins and co-factor of over 300 enzymes, takes part in a wide range of processes connected with cellular metabolism, including, among others, DNA synthesis, cells division and differentiation, communication between cells and immunological processes (Vallee and Auld 1990; Vallee and Falchuk 1993; Takeda 2000). Zinc ions cannot cross the biological membranes by passive diffusion, and zinc homeostasis, which is essential for correct functioning of the organism, is maintained by metallothioneins (MTs) and transmembrane transporters (Hojyo and Fukada 2016; Hara et al 2017). …”

“…Zinc transporters are divided into two groups: the solute-linked carrier 30 (SLC 30) protein family of zinc transporters (marked in the mammals from ZnT1 to ZnT10) and the Zip (Zrt- and Irt-like proteins) family (solute-linked carrier 39-SLC39) (Hara et al 2017). First of them take place in the transport of zinc ions from cytoplasm into the lumen of organelles or extracellular space.…”