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28.3: Activation of Integrins

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Cell Biology

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Activation of Integrins

28.3: Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."

In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus. As the cell encounters various extracellular signals, activated integrins affect cellular properties such as cell polarity, cytoskeletal structure, adhesion, migration, invasion, gene expression, cell survival, and proliferation.

"Inside-out signaling" depends on intracellular activators such cytoskeletal adaptor proteins like talin or kindlins. Talins contain binding sites for the β integrin cytosolic domains, a highly conserved C-terminal actin-binding site, and a Vinculin-binding site. Kindlin includes β integrin cytosolic tail binding sites in their F3 domains, membrane-binding domains, and a C-terminus that interacts with integrins, actin adaptor proteins, or integrin-linked kinase (ILK). Kindlin interacts with the β integrin cytoplasmic domain and stabilizes the integrin complex's activated state. “Inside-out signaling” can strengthen integrin-mediated adhesion with extracellular ligands, which transfer the necessary force for cell migration, invasion, ECM assembly, and remodeling.

Adapted from Section 9.1 Signaling molecules and cellular receptors, Openstax Biology for AP

Suggested Reading


Integrins Ligands Activation Outside-in Signaling Inside-out Signaling Extracellular Space Conformational Change Cell Membrane Stimulus Cell Polarity Cytoskeletal Structure Adhesion Migration Invasion Gene Expression Cell Survival Proliferation Intracellular Activators Talin Kindlins Binding Sites Actin-binding Site Vinculin-binding Site Membrane-binding Domains Integrin-linked Kinase (ILK) Integrin Complex

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