Chemokine receptor
Chemokine receptor
Chemokine receptors are a type of G protein-coupled receptor (GPCR) found on the surface of certain cells. They play a crucial role in the immune system by directing the movement of leukocytes (white blood cells) to sites of inflammation, infection, and injury. These receptors are activated by chemokines, which are small signaling proteins secreted by cells in response to various stimuli.
Structure
Chemokine receptors are characterized by their seven transmembrane domains, a hallmark of GPCRs. The extracellular N-terminus and three extracellular loops are involved in ligand binding, while the intracellular C-terminus and three intracellular loops interact with G proteins to transduce signals inside the cell.
Function
The primary function of chemokine receptors is to mediate the effects of chemokines. Upon binding to their specific chemokines, these receptors activate intracellular signaling pathways that lead to various cellular responses, including:
- Chemotaxis: The directed movement of cells towards higher concentrations of chemokines.
- Cell adhesion: Enhancing the ability of leukocytes to adhere to the endothelium and migrate into tissues.
- Cell activation: Triggering the activation of leukocytes, which can lead to the release of cytokines and other inflammatory mediators.
Types of Chemokine Receptors
Chemokine receptors are classified into four main families based on the structure of their ligands:
- CXC receptors (CXCR): These receptors bind to CXC chemokines, which have a single amino acid separating the first two cysteines.
- CC receptors (CCR): These receptors bind to CC chemokines, which have adjacent cysteines.
- CX3C receptors (CX3CR): These receptors bind to CX3C chemokines, which have three amino acids between the first two cysteines.
- XC receptors (XCR): These receptors bind to XC chemokines, which lack the first and third cysteines.
Clinical Significance
Chemokine receptors are involved in a variety of physiological and pathological processes. They are critical in the development and function of the immune system, but they also play roles in:
- Cancer: Some chemokine receptors are involved in tumor growth and metastasis.
- HIV infection: Certain chemokine receptors, such as CCR5 and CXCR4, serve as co-receptors for HIV entry into cells.
- Autoimmune diseases: Aberrant chemokine receptor signaling can contribute to the pathogenesis of diseases like rheumatoid arthritis and multiple sclerosis.
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