Copper Transporter (Solute Carrier Family 31)

The SLC31 (CTR) family of copper transporters consists of two members of human, CTR1, and CTR2, which are encoded in the human genome by the SLC31A1 and SLC31A2 genes, respectively. They are expressed in all tissues and organs examined, with high levels in the liver and kidney. Excess copper accumulation in cells over-expressing human CTR1 indicates that it is a limiting factor for cellular copper acquisition. However, unlike CTR1, human CTR2 expression levels do not result in significant changes in cellular copper metabolism.

One to six SLC31 family members have been identified in each eukaryote with some subcellular and/or organ specificities. The subcellular localization of CTR1 is different in mammalian cell lines. Most of the CTR1 in human embryonic kidney (HEK 293) cells are localized at the plasma membrane such as yCTR1 in yeast. However, in some cell lines, including lung cancer cell lines (A549 and H441), and hepatocellular carcinoma cell line (HepG2), CTR1 is predominantly in the cytoplasmic vesicular compartments.

(A) Localization of ZnT transporters in a generalized mammalian cell. (B) Localization of ZnT transporters in an intestinal epithelial cell. (C) Localization of ZnT transporters in a secreting mammary epithelial cell. (D) Localization of ZnT3 in an axon terminal. Organelles of the cell are labeled in the panel A. Arrows indicate the direction of translocation of zinc ions. Fig.1 Schematic illustration of the structure, subcellular localization, and function of human CTR1. (Kim, 2013)

Copper is an important mineral in many organisms, but it is highly toxic, as demonstrated by serious health concerns related to its deficiency or excess accumulation. The SLC31 family of copper transporters is the primary gateway of copper acquisition in eukaryotes, from yeast to humans. Function, modes of action, and regulation of CTR and other molecular factors have revealed that organisms have evolved fascinating mechanisms for tight control of copper metabolism. These factors functionally cooperate with CTR for copper transport, compartmentalization, incorporation into cuproproteins, and detoxification.

Human SLC31 (CRT) Family Members
SLC31A1	SLC31A2

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Reference

Kim H, et al. (2013). SLC31 (CTR) family of copper transporters in health and disease. Mol Aspects Med. 34(2-3): 561-70.

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