Integrininactivating

Integrins are transmembrane receptors that mediate cell adhesion to the extracellular matrix and to other cells. They function as αβ heterodimers and can switch between conformations that determine ligand affinity. The bent, closed form is low-affinity (inactive), while the extended, open form is high-affinity (active). Integrin inactivation describes mechanisms that maintain or shift integrins toward the low-affinity state, reducing adhesion and signaling.

Multiple processes promote inactivation. Inside-out signals and cytoskeletal remodeling can disrupt talin and kindlin interactions with the β subunit, favoring the closed conformation. Endocytosis and recycling remove surface integrins, lowering receptor density. Proteolytic shedding of ectodomains and post-translational modifications can permanently or temporarily diminish functional receptors. Pharmacologic agents or antibodies can also lock integrins in a low-affinity state to suppress activity.

Physiologically, integrin inactivation helps regulate leukocyte extravasation, platelet function, and tissue remodeling by preventing excessive adhesion. Pathologically, impaired inactivation or excessive deactivation can contribute to disease, including impaired wound healing, chronic inflammation, cancer metastasis, or thrombosis. Therapeutic approaches sometimes aim to promote integrin inactivation or stabilize low-affinity states, including integrin antagonists and antibodies that hinder activation or promote receptor removal.

Assessment of integrin inactivation relies on conformation-sensitive antibodies, ligand-binding assays, flow cytometry, and imaging to evaluate affinity states and receptor surface levels. While the term integrin inactivation is less common than activation, it describes the cellular and pharmacologic mechanisms that reduce integrin-mediated adhesion.