Copper is an element essential for life, but excessive copper can be toxic or even lethal to the cell. Therefore, cells have
developed sophisticated ways to maintain a critical copper balance, with the intake, export, and intracellular
compartmentalization or buffering of copper strictly regulated. In S. cerevisiae, the 3 copper uptake genes CTR1, CTR2, and CTR3 have been identified. In
mammals, however, the molecular basis for copper uptake is unknown. Zhou and Gitschier (1997) isolated a human cDNA
encoding COPT1, which they called CTR1, by functional complementation of the yeast high-affinity copper uptake mutant ctr1.
The deduced 190-amino acid human CTR1 protein is similar to yeast CTR1 and Arabidopsis COPT1, a copper transporter
also isolated by functional complementation of yeast ctr1. All 3 predicted proteins have 3 transmembrane domains and an N
terminus that is rich in methionine and serine residues; the N terminus of human CTR1 is also abundant in histidines.
NCBI Summary:
The protein encoded by this gene is a high-affinity copper transporter found in the cell membrane. The encoded protein functions as a homotrimer to effect the uptake of dietary copper. [provided by RefSeq, Aug 2011]
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
Comment
Kuo YM, et al 2001 reported that the copper transporter CTR1 provides an essential function in mammalian
embryonic development.
The authors observe early embryonic lethality in homozygous mutant embryos and a deficiency in copper
uptake in the brains of heterozygous animals. Ctr1(-/-) embryos can be recovered at E8.5 but
are severely developmentally retarded and morphologically abnormal. Histological analysis
reveals discontinuities and variable thickness in the basement membrane of the embryonic region
and an imperfect Reichert's membrane, features that are likely due to lack of activity in the
collagen cross-linking cupro-enzyme lysyl oxidase. A study of the spatial and temporal
expression pattern of Ctr1 during mouse development and adulthood further shows that CTR1 is
ubiquitously transcribed with highest expression observed in the specialized epithelia of the
choroid plexus and renal tubules and in connective tissues of the eye, ovary, and testes.
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
The copper transporter (SLC31A1/CTR1) is expressed in bovine spermatozoa and oocytes: Copper in IVF medium improves sperm quality. Anchordoquy JP et al. (2017) Adequate dietary intake of copper (Cu) is required for normal reproductive performance in cattle. The objective of this study was to investigate the pregnancy rates from cattle with deficient, marginal and adequate Cu plasma concentration at the beginning of artificial insemination protocol. Moreover, we determined Cu concentrations present in bovine oviductal fluid (OF), and the effects of Cu on fertilizing ability of bovine spermatozoa. Also, the presence of Cu transporter, SLC31A1 (also known as CTR1), in spermatozoa and in vitro matured oocyte were investigated. We found no differences in pregnancy rates among animals with adequate, marginal, and deficient Cu concentrations measured in plasma at the beginning of fixed-time artificial insemination (FTAI) protocol. Copper concentrations in OF were 38.3 ± 2.17 μg/dL (mean ± SEM) regardless of cupremia levels. The addition of 40 μg/dL Cu to IVF medium enhanced total and progressive motility, sperm viability, functional sperm membrane integrity (HOST), sperm-zona binding, and pronuclear formation. On the other hand, the presence of Cu in IVF medium did not modify acrosome integrity and cleavage rates after IVF, but impaired blastocyst rates. Cu transporter SLC31A1 was detected in bovine spermatozoa in the apical segment of acrosome, and in the oocyte matured in vitro. In conclusion, the results obtained in the present study determined that cupremia levels at the beginning of FTAI protocol did not influence the pregnancy rates at 60 d after insemination. The presence of CTR1 in bovine mature oocyte and spermatozoa, as well as the beneficial effect of Cu on sperm quality would suggest an important role of this mineral during the fertilization process.//////////////////