The Families of Zinc (SLC30 and SLC39) and Copper (SLC31) Transporters

The solute carriers families 30 (SLC30; ZnT), 39 (SLC39; ZIP), and 31 (SLC31; CTR) are involved in the essential maintenance of cellular zinc (Zn2 +) and copper (Cu2 +) homeostasis, respectively. ZnTs mediate Zn2 + extrusion from cells (SLC30A1) or transport Zn2 + into organelles and secretory vesicles/granules (SLC30A2–SLC30A8). SLC39 family members are predominantly localized to the cell membrane where they perform Zn2 + uptake and increase the availability of cytosolic Zn2 +. SLC39A1 is ubiquitously expressed, whereas other ZIP transporters (e.g., SLC39A2 and SLC39A3) show a more tissue-restricted expression consistent with organ-specific functions of these proteins. The members A1 (CTR1) and A2 (CTR2) of the SLC31 family of solute carriers belong to a network of proteins that acts to regulate the intracellular Cu2 + concentration within a certain range. SLC31A1 is predominantly localized to the plasma membrane, whereas SLC31A2 is mainly found in intracellular membranes of the late endosome and lysosome. The specific function of SLC31A2 is not known. SLC31A1 is ubiquitously expressed and has been characterized as a high-affinity importer of reduced copper (Cu+). Cu2 + transport function of CTR proteins is associated with oligomerization; SLC31A1 trimerizes and thereby forms a channel-like structure enabling Cu2 + translocation across the cell membrane. The molecular characteristics and structural details (e.g., membrane topology, conserved Zn2 +, and Cu2 + binding sites) and mechanisms of translational and posttranslational regulation of expression and/or activity have been described for SLC30 and SLC39 family members, and for SLC31A1. For SLC31A1, data on tissue-specific functions (e.g., in the intestine, heart, and liver) are also available. A link between SLC31A1, immune function, and disorders such as Alzheimer's disease or cancer makes the protein a candidate therapeutic target. In secretory tissues (e.g., the mammary gland and pancreas), Zn2 + transporters of SLC families 30 and 39 are involved in specific functions such as insulin synthesis and secretion, metallation of digestive proenzymes, and transfer of nutrients into milk. Defective or dysregulated Zn2 + metabolism in these organs is associated with disorders such as diabetes and cancer, and impaired Zn2 + secretion into milk.