Integrins Lecture Notes

This set of flashcards covers key concepts, structures, functions, and clinical implications of integrins as discussed in the lecture notes.

What is an Integrin?

Integrins are transmembrane proteins that facilitate cell adhesion and communication.

What is the structure of integrins?

Integrins consist of two subunits, alpha (α) and beta (β), which form a heterodimer.

What domains are included in the integrin structure?

Integrins have several domains including: A-B domain, B-Propeller domain, Hybrid domain, Transmembrane domain, and Cytoplasmic domain.

What role do integrins play in haemostasis?

Integrins are crucial for platelet aggregation and adhesion during the formation of a blood clot.

How does integrin activation occur?

Integrin activation is triggered by agonist stimulation and leads to changes in ligand-binding affinity.

What are the two states of integrins?

Integrins can exist in a low-affinity state and a high-affinity state.

What is the significance of the low-affinity state of integrins?

The low-affinity state prevents platelet aggregation and thrombosis.

What factors can stimulate inside-out signaling for integrins?

Factors like talin and kindlin can activate integrins by binding to them and changing their conformation.

What is the role of the cytoskeleton in integrin function?

Cytoskeletal dynamics are crucial for integrin-mediated adhesion, spreading, and retraction.

What role do platelets play in inflammatory response?

Platelets help recruit leukocytes to sites of injury and inflammation.

What is Glanzmann's thrombasthenia?

Glanzmann's thrombasthenia is a bleeding disorder caused by a defect in integrin αIIbβ3.

What is the inside-out signaling mechanism?

Inside-out signaling involves intracellular signals leading to conformational changes in integrins, enhancing ligand-binding affinity.

What is outside-in signaling?

Outside-in signaling refers to processes initiated by ligand binding to integrins, leading to intracellular responses.

Why is integrin clustering important?

Clustering increases integrin avidity and enhances cell adhesion and signaling.

What is the coagulation cascade?

The coagulation cascade is a series of biochemical reactions that lead to blood clotting, activated by thrombin.

How do platelets activate during injury?

Activated platelets release ADP and thromboxane, which further activate and aggregate surrounding platelets.

What happens during thrombus formation?

Platelets aggregate and stabilize a clot through integrin interactions with fibrinogen and other components.

What is the role of phosphatidylserine in platelets?

Phosphatidylserine exposure on the surface of activated platelets provides a negative surface for coagulation proteins.

What factors influence integrin expression?

Integrin expression is highly regulated and can change due to inflammatory signals.

What is leukocyte adhesion deficiency (LAD)?

LAD is a genetic disorder that impairs leukocyte integrin function, leading to immune deficiency.

What role do selectins play in leukocyte trafficking?

Selectins mediate the initial tethering and rolling of leukocytes along the endothelium.

How do integrins assist in leukocyte transmigration?

Integrins allow leukocytes to adhere to and migrate through the endothelial barrier during inflammation.

What is the significance of the 'salt bridge' in integrins?

The salt bridge between specific amino acids stabilizes the integrin structure and influences signaling.

What are the consequences of integrin mutations?

Integrin mutations can lead to bleeding disorders, impaired leukocyte function, and increased susceptibility to infections.

What types of drugs target integrins?

Anti-integrin drugs include monoclonal antibodies and small-molecule inhibitors used in thrombosis and inflammation treatment.

What is the mechanism of action for PROTACs?

PROTACs are bifunctional molecules that promote targeted protein degradation by bringing together the target protein and E3 ligase.

What is the role of BTK in platelet function?

Bruton’s tyrosine kinase (BTK) is involved in signaling pathways that regulate platelet activation and aggregation.

How do antiplatelet drugs affect integrins?

Antiplatelet drugs inhibit integrin function, preventing platelet aggregation and thrombus formation.

What role does aging play in integrin function?

Aging can lead to reduced integrin expression and increased risk of thrombotic events.

What are the potential side effects of anti-integrin therapies?

Anti-integrin therapies can lead to bleeding risks and complications in wound healing.

What is the significance of the integrin β3 subunit?

The β3 subunit is critical for platelet activation and aggregation.

What impact does IL-1β have on endothelial cells?

IL-1β can stimulate the expression of ICAM-1 and VCAM-1, promoting leukocyte adhesion.

What is the role of integrins in wound healing?

Integrins facilitate cell migration and re-epithelialization during the wound healing process.

What does RGD represent in terms of integrins?

RGD (Arginine-Glycine-Aspartic acid) is a peptide sequence that mimics the binding site of integrins.

What do increased levels of D-dimer indicate?

Increased D-dimer levels can indicate thrombus formation or clot degradation in various clinical conditions.

What is the function of P-selectin?

P-selectin mediates the adhesion of leukocytes to activated endothelium during inflammation.

How does SARS-CoV-2 interact with platelets?

SARS-CoV-2 can activate platelets via the ACE2 receptor, contributing to thrombotic complications.

What is fibronectin's role in cell adhesion?

Fibronectin acts as a bridge between integrins on cells and components of the extracellular matrix.

What mechanism allows platelets to participate in thrombus formation?

Platelets activate and aggregate through integrin interactions with fibrinogen and other adhesive molecules.

What is the effect of thromboxane A2 (TXA2) on platelets?

TXA2 enhances platelet activation and aggregation.

What is the relationship between integrins and metastasis?

Integrins are involved in cancer cell adhesion, migration, and invasion, contributing to metastasis.

What occurs during the 'spreading' phase of platelet function?

During spreading, platelets extend their membrane and create more contacts with the substrate.

What are the characteristics of integrin α4β7?

Integrin α4β7 is involved in the adhesion of leukocytes to gut endothelial cells.

What happens during integrin-mediated outside-in signaling?

It leads to cell spreading, cytoskeletal reorganization, and activation of cellular pathways.

What is the role of integrins in atherosclerosis?

Integrins contribute to plaque formation by mediating the adhesion and migration of inflammatory cells.

How do integrins participate in angiogenesis?

Integrins help promote endothelial cell migration and capillary tube formation during new vessel formation.

What is the effect of calcium ions on integrin activation?

Calcium ions are crucial for integrin activation and function in platelet aggregation.

What are common therapeutic applications for anti-integrin drugs?

Anti-integrin drugs are used for conditions like inflammatory diseases, and cardiovascular events.

Describe 'inside-out' signaling in integrins.

Inside-out signaling refers to intracellular signals that result in the activation and clustering of integrins.

How is integrin activity related to immune response?

Integrin activity is essential for leukocyte trafficking and activation during immune responses.

What is the role of talin in integrin activation?

Talin binds to the cytoplasmic tail of integrins, triggering conformational changes that enhance affinity.

What happens during thrombus consolidation?

During consolidation, a stable fibrin network is formed, which strengthens the clot.

What experimental models are used to study integrins?

Animal models and in vitro assays using platelet-rich plasma are common for studying integrins.

What is the significance of αIIbβ3 integrin in platelets?

αIIbβ3 is critical for platelet aggregation as it binds fibrinogen and other ligands.

What impact does HIV have on integrin expression?

HIV can manipulate integrin expression on immune cells, affecting their function.

What are the implications of targeting integrins for cancer therapy?

Targeting integrins can disrupt the microenvironment of tumors and inhibit metastasis.

What does the term 'vicious cycle' imply in the context of platelet-leukocyte interaction?

It refers to the continuous activation of platelets and leukocytes, worsening inflammation and thrombosis.

What influence do cytokines have on integrin expression?

Cytokines can upregulate integrin expression on leukocytes, enhancing their adhesion and migration.

Identify a common assay used to study integrin function.

The platelet aggregation assay is commonly used to examine integrin activity.

How does integrin expression vary among different cell types?

Integrin expression is distinct among cell types, reflecting their specific functions and roles.

What is the role of integrins in tissue repair?

Integrins facilitate cell migration and interaction with the extracellular matrix during tissue repair.

Explain how shear stress affects integrin activation.

Shear stress can enhance integrin affinity and promote platelet adhesion in circulating blood.

What clinical conditions are associated with integrin dysfunction?

Conditions like thrombosis, bleeding disorders, and autoimmune diseases are linked with integrin dysfunction.

What relevance does integrin research have in COVID-19?

Integrins play a role in the pathogenic response to COVID-19, influencing thrombotic complications.

Describe integrin dimerization.

Integrin dimerization involves the pairing of α and β subunits, essential for their functional activity.

What is the potential for PROTACs in future therapies?

PROTACs hold promise for targeted degradation of specific proteins involved in diseases.

What is the role of membrane lipids in integrin function?

Membrane lipids influence integrin structure and its interactions with other proteins.

What do integrins help regulate within the immune system?

Integrins help regulate leukocyte adhesion, migration, and activation in immune responses.

Discuss the effect of thrombin on integrins.

Thrombin can activate integrins, enhancing platelet aggregation during clot formation.

What happens during the process of leukocyte extravasation?

Leukocytes adhere to the endothelium, migrate between cells, and enter tissues during inflammation.

Describe the importance of integrin expression levels in cancer metastasis.

High integrin expression can promote cancer cell adhesion and invasion, leading to metastasis.

How do integrins affect endothelial function?

Integrins modulate endothelial cell adhesion, permeability, and inflammatory responses.