Integrin Beta-3 (ITGB3, also known as CD61) is a transmembrane receptor that pairs with ITGAV (αV) to form the αVβ3 integrin (Vitronectin receptor). This integrin is expressed on platelets, microglia, and [neurons](/entities/neurons), where it mediates interactions with the extracellular matrix and plays roles in platelet aggregation, phagocytosis, and synaptic plasticity.
Structure
ITGB3 is a type I transmembrane protein:
Extracellular domain: Contains cysteine-rich repeats and ligand-binding sites
Transmembrane domain: Single pass helix
Cytoplasmic tail: Interacts with cytoskeletal proteins and signaling molecules
ITGB3 primarily pairs with ITGAV to form αVβ3 integrin, and with ITGA2B to form GPIIb/IIIa on platelets.
Normal Function
In the nervous system:
Platelet function: Mediates platelet aggregation and thrombosis
Microglial phagocytosis: Engages vitronectin and other ligands for phagocytosis
Synaptic plasticity: Involved in activity-dependent synaptic remodeling
Cell migration: Guides neuronal and glial migration
Role in Neurodegeneration
Alzheimer's Disease
Expressed on microglia surrounding [Aβ](/proteins/amyloid-beta) plaques
Mediates microglial Aβ phagocytosis via vitronectin bridging
αVβ3 promotes Aβ-induced inflammatory signaling
Genetic variants associated with AD risk in some populations
Molecular Mechanisms in AD
Aβ clearance pathway: αVβ3 integrin on microglia binds Aβ-VTN complexes, facilitating phagocytosis. Genetic variants in ITGB3 can impair this clearance, contributing to plaque accumulation[@bitens2019]
Pro-inflammatory signaling: Aβ engagement of αVβ3 triggers NF-κB activation and pro-inflammatory cytokine release
Synaptic remodeling: αVβ3 participates in activity-dependent synaptic plasticity; dysregulation contributes to synaptic loss