Integriinien

Integriinien are a family of transmembrane receptors that mediate cell–extracellular matrix adhesion and, in some contexts, cell–cell interactions. They are heterodimers composed of an alpha and a beta subunit, and in humans there are 18 alpha (ITGA) and 8 beta (ITGB) subunits, which combine to form at least 24 distinct integrins. Their ligand diversity includes fibronectin, collagen, laminin, and vitronectin, enabling adhesion to a wide range of tissue matrices.

Integrins function in bidirectional signaling. Outside–in signaling transduces information from the extracellular environment to the cytoskeleton, influencing cell survival, proliferation, and migration via pathways such as FAK/Src. Inside–out signaling modulates integrin affinity and avidity through intracellular adaptor proteins like talin and kindlin, enabling rapid changes in adhesion strength during processes like migration.

Structural activation involves conformational changes from a bent, low-affinity state to an extended, high-affinity state, modulated by divalent cations such as calcium and magnesium. Activated integrins cluster into focal adhesions that link to actin filaments, coordinating cytoskeletal remodeling and cell movement.

Biological roles of integriinien are broad, encompassing development, tissue organization, immune cell trafficking, wound healing, and angiogenesis. In disease, integrins contribute to cancer cell invasion and metastasis, fibrosis, inflammatory and autoimmune conditions, and thrombotic disorders, with platelet integrins playing crucial roles in hemostasis.

Therapeutically, integrins are targets of antibodies and small molecules in various conditions. Examples include therapies that block specific alpha integrins to treat inflammatory diseases, as well as platelet integrin antagonists used to influence thrombosis risk. Research employs knockout models, flow cytometry, imaging, and structural biology to elucidate their functions and regulation.