The SLC31A1 gene is a fundamental component of cellular machinery, directing the production of a protein that facilitates a basic and widespread biological process. This gene and its product are involved in maintaining a delicate balance within cells, which is important for overall biological stability, impacting how cells acquire and manage an indispensable element required for various bodily functions.
What is SLC31A1?
The SLC31A1 gene creates the Human Copper Transporter 1 (CTR1). This protein is situated within the cell membrane. Its primary role is to allow copper to enter cells. Copper is an indispensable trace element for the body, participating in numerous biological reactions and cellular activities. Without proper copper levels, many bodily functions would be compromised.
SLC31A1’s Role in Copper Transport
CTR1 facilitates the movement of copper ions across the cell membrane through a mechanism that involves high affinity for copper. The protein forms a channel or pore, allowing copper ions to pass into the cell.
Efficient copper transport into cells is important for a variety of cellular processes. Copper serves as a cofactor for many enzymes, including cytochrome c oxidase, which is involved in energy production within mitochondria, and superoxide dismutase, which helps protect cells from oxidative damage.
CTR1’s activity ensures that cells receive the necessary copper to support these enzymatic reactions. The proper function of CTR1 is important for supplying copper to key intracellular enzymes involved in processes such as respiration, oxidative stress protection, iron metabolism, and hormone synthesis.
SLC31A1 and Human Health Conditions
When the function of SLC31A1 or its encoded protein, CTR1, is impaired, there can be direct consequences for human health. Rare genetic mutations in SLC31A1 can lead to syndromes characterized by severe copper deficiency or dysregulation, particularly affecting the central nervous system.
For instance, mutations have been identified in infants with distinctive syndromes involving infantile seizures and neurodegeneration, indicating profound central nervous system copper deficiency. Another reported case involved a newborn with a pathogenic variant in SLC31A1, leading to severe respiratory distress, multifocal brain hemorrhages, and very low serum copper levels, ultimately resulting in death.
Altered CTR1 expression, whether an increase or decrease, can contribute to the progression of certain diseases where copper dyshomeostasis is observed. In some cancers, copper levels are often elevated, and high expression of copper transport proteins like SLC31A1 can facilitate copper uptake, potentially leading to a type of cell death. Conversely, in neurodegenerative conditions, maintaining the delicate balance of copper through proper CTR1 function is important, as disruptions can contribute to various health issues, impacting cellular metabolism.
SLC31A1 in Medical Treatments
CTR1 plays a significant role in the uptake of platinum-based chemotherapy drugs into cancer cells. These drugs, such as cisplatin, carboplatin, and oxaliplatin, are highly polar and do not easily diffuse across the cell membrane, relying on transporters like CTR1 for entry.
Studies have shown that increased expression of CTR1 leads to enhanced uptake of cisplatin and its analogues. Variations in CTR1 expression or function can influence the effectiveness and side effects of these anti-cancer treatments.
For example, some cisplatin-resistant cancer cell lines exhibit reduced CTR1 expression, contributing to their resistance to the drug. Conversely, elevated CTR1 expression has been associated with improved therapeutic responses in ovarian carcinoma patients receiving platinum-based chemotherapy, suggesting CTR1 levels could serve as a predictor of treatment outcome.
Research is exploring the potential of CTR1 as a therapeutic target to improve drug delivery or overcome drug resistance in cancer therapy. Strategies to modulate CTR1 expression, such as increasing its levels, could enhance the accumulation of platinum drugs in cancer cells, thereby improving treatment efficacy. For instance, combining cisplatin with a copper chelator has been shown to increase cisplatin-DNA adduct levels and improve therapeutic outcomes in mouse models, demonstrating the potential to manipulate copper levels and, in turn, CTR1 activity to enhance cancer treatment.