VLA-4

VLA-4

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Diagram of VLA-4 structure

VLA-4 (Very Late Antigen-4) is an important integrin involved in various cellular processes, including cell adhesion, immune response, and cell signaling. It is a heterodimeric protein composed of two subunits, _4 (CD49d) and _1 (CD29), which are non-covalently associated.

Structure

VLA-4 is a member of the integrin family, which are transmembrane receptors that facilitate cell-extracellular matrix (ECM) adhesion. The _4 subunit pairs with the _1 subunit to form the VLA-4 integrin. The extracellular domain of VLA-4 binds to its ligands, while the cytoplasmic domain interacts with the cell's cytoskeleton and signaling molecules.

Function

VLA-4 plays a crucial role in the immune system, particularly in the trafficking of leukocytes to sites of inflammation. It mediates the adhesion of leukocytes to the endothelium by binding to its primary ligand, VCAM-1 (Vascular Cell Adhesion Molecule-1), which is expressed on activated endothelial cells. This interaction is essential for the transmigration of leukocytes from the bloodstream into tissues.

Clinical Significance

VLA-4 is a target for therapeutic intervention in various autoimmune diseases and inflammatory disorders. Inhibitors of VLA-4, such as natalizumab, are used in the treatment of multiple sclerosis and Crohn's disease. These inhibitors block the interaction between VLA-4 and VCAM-1, reducing the migration of inflammatory cells into the central nervous system and the gastrointestinal tract, respectively.

Related Pages

• Integrin
• Cell adhesion
• Immune system
• Leukocyte
• VCAM-1
• Multiple sclerosis
• Crohn's disease