regulation of cell adhesion mediated by integrin

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate, or extent of cell adhesion mediated by integrin. [GOC:add]

Integrin-mediated cell adhesion is a complex and tightly regulated process that plays a critical role in numerous biological processes, including cell migration, tissue development, immune response, and wound healing. Integrins are transmembrane receptors that act as crucial mediators of cell-cell and cell-extracellular matrix (ECM) interactions. The regulation of integrin-mediated cell adhesion involves a multifaceted interplay of signaling pathways, cytoskeletal rearrangements, and external cues.

**1. Ligand Binding and Conformational Changes:**

* The process begins with the binding of an ECM ligand, such as fibronectin, collagen, or laminin, to the extracellular domain of the integrin. This binding event triggers a conformational change within the integrin molecule, leading to its activation.
* The integrin undergoes a shift from a bent, inactive conformation to an extended, active conformation. This conformational change exposes the binding sites for intracellular signaling proteins, initiating downstream signaling cascades.

**2. Inside-Out Signaling and Activation:**

* The binding of intracellular proteins to the cytoplasmic tail of the integrin triggers "inside-out signaling." This signaling pathway involves the activation of various kinases, including focal adhesion kinase (FAK) and Src kinases.
* These kinases phosphorylate key residues on the integrin cytoplasmic domain, further promoting its activation and increasing its affinity for the ECM ligand.

**3. Outside-In Signaling and Cellular Responses:**

* Once the integrin is activated, it transmits signals from the ECM to the cell's interior, known as "outside-in signaling." This signaling pathway involves the recruitment of various adaptor proteins and signaling molecules to the integrin complex, forming a structure called the focal adhesion.
* These focal adhesions serve as platforms for the assembly of the cytoskeleton, including actin filaments, microtubules, and intermediate filaments. The cytoskeletal reorganization driven by integrin signaling enables cells to adhere, spread, migrate, and exert forces on their surroundings.

**4. Regulation by Cytoskeletal Dynamics:**

* Integrin signaling and cytoskeletal dynamics are intimately intertwined. Actin filaments, which are essential for cell adhesion and migration, are dynamically regulated by integrins.
* Integrin activation leads to the polymerization and depolymerization of actin filaments, enabling cells to form lamellipodia and filopodia, which are essential for cell motility.

**5. Modulation by External Factors:**

* The regulation of integrin-mediated cell adhesion is influenced by a wide range of external factors, including:
* **Growth factors:** Growth factors, such as platelet-derived growth factor (PDGF) and epidermal growth factor (EGF), can activate intracellular signaling pathways that stimulate integrin activation and adhesion.
* **Cytokines:** Cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), can modulate integrin expression and activity, influencing immune cell responses.
* **Extracellular matrix components:** The composition and density of the ECM can influence integrin affinity and cell adhesion.

**6. Regulation by Integrin Clustering:**

* Integrin clustering plays a crucial role in regulating cell adhesion. When multiple integrins cluster together, they form larger adhesion complexes, increasing their signaling capacity and enhancing cell adhesion.
* Integrin clustering can be promoted by various factors, including ECM ligands, intracellular signaling molecules, and cytoskeletal components.

**7. Regulation by Integrin Turnover:**

* The dynamics of integrin turnover, including their endocytosis and recycling, are essential for regulating cell adhesion.
* Integrins can be internalized through endocytosis and recycled back to the cell surface, allowing for the continuous modulation of cell adhesion and migration.

**8. Role in Pathological Conditions:**

* Dysregulation of integrin-mediated cell adhesion is implicated in various pathological conditions, including cancer, inflammation, and cardiovascular disease.
* In cancer, altered integrin expression and signaling can promote tumor cell invasion, metastasis, and angiogenesis.

**In summary, the regulation of cell adhesion mediated by integrin is a complex process involving a intricate interplay of signaling pathways, cytoskeletal rearrangements, and external cues. This tightly controlled mechanism is essential for diverse cellular functions and plays a crucial role in maintaining tissue integrity, mediating cellular responses to environmental changes, and ensuring proper immune function.'
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Proteins (7)

Compounds (397)