| Gene |
[ITGB3](/genes/itgb3) |
| UniProt |
P05106 |
| PDB |
1T6P, 3T0P |
| Mol. Weight |
91 kDa |
| Localization |
Cell surface (platelets, [microglia](/cell-types/microglia-neuroinflammation), neurons) |
| Family |
Integrin beta family |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Stroke |
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, where it mediates interactions with the extracellular matrix and plays roles in platelet aggregation, phagocytosis, and synaptic plasticity.
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.
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
- Expressed on microglia surrounding Aβ plaques
- Mediates microglial Aβ phagocytosis via vitronectin bridging
- αVβ3 promotes Aβ-induced inflammatory signaling
- Genetic variants associated with AD risk in some populations
- 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
- 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
In PD, αVβ3 mediates:
- Recognition and phagocytosis of extracellular α-synuclein aggregates
- Activation of NLRP3 inflammasome in microglia
- Blood-brain barrier breakdown via matrix metalloproteinase activation
¶ Stroke and Vascular Dementia
- Central to platelet-mediated thrombus formation
- ITGB3 antagonists reduce ischemic damage in models
ITGB3 as therapeutic target:
- αVβ3 antagonists for reducing Aβ-induced inflammation
- Anti-ITGB3 antibodies to modulate microglial activation
- Integrin-targeted drug delivery across the BBB
flowchart TD
A["Aβ or α-Synuclein"] --> B["VTN Binding"]
B --> C["Aβ-VTN Complex"]
C --> D["αVβ3 Integrin<br/>Engagement"]
D --> E["Phagocytosis"]
D --> F["NF-κB Activation"]
F --> G["Pro-inflammatory<br/>Cytokines"]
G --> H["Neuroinflammation"]
I["Platelet Activation"] --> J["ITGB3/GPIIbIIIa"]
J --> K["Thrombus Formation"]
K --> L["Ischemic Damage"]
style A fill:#e1f5fe,stroke:#333
style E fill:#e1f5fe,stroke:#333
style G fill:#ffcdd2,stroke:#333
style L fill:#ffcdd2,stroke:#333
- αVβ3 integrin in AD microglia (Milan et al., 2021)
- ITGB3 and platelet function in neurodegeneration (Jellinger et al., 2020)
- Integrin signaling in neuroinflammation (Plow et al., 2019)
- ITGB3 variants and AD risk (Bitens et al., 2019)
- Integrin-mediated Aβ clearance (Berco et al., 2018)
- Integrins in PD neuroinflammation (Dorote et al., 2019)
- Microglial integrins in brain homeostasis (Feig et al., 2019)