Transferrin receptor

Transferrin receptor (TfR) is a cell membrane protein that plays a critical role in iron uptake and regulation in mammals. It is primarily involved in the control of cellular iron levels, which is essential for various biological processes such as hemoglobin synthesis, DNA synthesis, and cellular respiration. The transferrin receptor mediates the uptake of transferrin-bound iron into cells through a process known as receptor-mediated endocytosis.

Structure

The transferrin receptor is a transmembrane protein that exists mainly as a dimer on the cell surface. Each monomer consists of a large extracellular domain that binds transferrin, a single transmembrane domain, and a short cytoplasmic tail. The extracellular portion is responsible for the high-affinity binding of transferrin, which is a blood plasma protein that transports iron throughout the body.

Function

The primary function of the transferrin receptor is to facilitate the uptake of iron into cells. Iron is a vital mineral that is necessary for the production of red blood cells and is a component of various enzymes and proteins. However, free iron is toxic to cells, so its levels are tightly regulated in the body. The transferrin receptor binds to transferrin that is loaded with iron, and the complex is then internalized by the cell through receptor-mediated endocytosis. Once inside the cell, iron is released from transferrin in the acidic environment of the endosome, and the receptor-transferrin complex is recycled back to the cell surface, where transferrin is released to pick up more iron.

Regulation

The expression of the transferrin receptor is tightly regulated by cellular iron levels. When iron levels are low, cells increase the production of transferrin receptors to enhance iron uptake. Conversely, when iron levels are high, the number of transferrin receptors on the cell surface is reduced to prevent excess iron uptake. This regulation ensures that cells maintain optimal iron levels and prevent the toxic effects of iron overload.

Clinical Significance

Alterations in transferrin receptor function or expression can lead to various iron metabolism disorders, including iron deficiency anemia and hemochromatosis. Measurement of transferrin receptor levels in the blood can be used as a diagnostic tool to assess iron status and distinguish between different types of anemia.

Additionally, the transferrin receptor is overexpressed in many types of cancer cells, which require large amounts of iron to sustain rapid growth and proliferation. This has led to the development of therapeutic strategies that target the transferrin receptor to deliver cytotoxic agents selectively to cancer cells.

Related Pages

• Iron metabolism
• Transferrin
• Receptor-mediated endocytosis
• Iron deficiency anemia
• Hemochromatosis