| Gene |
[VTN](/genes/vtn) |
| UniProt |
P04004 |
| PDB |
1JPS, 1ATN |
| Mol. Weight |
75 kDa |
| Localization |
Extracellular matrix, plasma |
| Family |
Vitronectin family (ECM glycoprotein) |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers), [Atherosclerosis](/diseases/atherosclerosis) |
Vitronectin (VTN) is a multifunctional extracellular matrix glycoprotein found in plasma and tissues. It plays important roles in cell adhesion, migration, and immune regulation. In the brain, vitronectin is involved in synaptic function and has been implicated in Alzheimer's disease through its interactions with Aβ and its role in microglial phagocytosis.
VTN is a secreted glycoprotein:
- SMT domain: Somatomedin B domain (N-terminal)
- RGD sequence: Integrin-binding motif
- Heparin-binding domain: C-terminal region
- Hemopexin-like domain: Involved in collagen binding
VTN exists in two forms: native (single chain) and processed (two-chain form held by disulfide bonds).
In the nervous system:
- Cell adhesion: Mediates cell-ECM adhesion via integrin binding
- Synaptic function: Present at synapses, involved in synaptic organization
- Complement regulation: Inhibits complement-mediated cell lysis
- Wound healing: Promotes tissue repair and remodeling
- Accumulates in Aβ plaques
- Acts as bridging molecule for Aβ-microglia interaction via integrins
- Promotes Aβ aggregation in some contexts
- Vitronectin fragments found in AD brain
- Mediates complement activation in plaque vicinity
Vitronectin's role in AD involves multiple interconnected pathways:
- Aβ-VTN-integrin complex formation: VTN binds both Aβ and integrin receptors (particularly αVβ3 and αVβ5), forming a molecular bridge that facilitates Aβ internalization by microglia
- Complement activation: VTN contributes to local complement cascade activation near plaques via C1q binding, enhancing neuroinflammation
- Peripheral clearance: VTN-Aβ complexes can be cleared via peripheral phagocytosis, potentially serving as a sink for cerebral Aβ
- Synaptic toxicity: VTN fragments interact with postsynaptic receptors, contributing to synaptic dysfunction
Specific VTN cleavage products have been identified in AD brain tissue:
- N-terminal fragments generated by matrix metalloproteinases (MMPs)
- These fragments retain integrin-binding activity but lose complement-regulatory function
- Fragment accumulation correlates with disease severity
- Regulates microglial phagocytosis via integrin signaling
- Modulates complement activation
- VTN polymorphisms associated with AD risk
Targeting vitronectin:
- VTN-blocking agents to reduce Aβ plaque pathology
- Modified VTN peptides for therapeutic benefit
- Gene therapy approaches
flowchart TD
A["Aβ monomer"] --> B["VTN Binding"]
B --> C["Aβ-VTN Complex"]
C --> D["Integrin Engagement<br/>αVβ3/αVβ5"]
D --> E["Microglial Activation"]
E --> F["Phagocytosis"]
C --> G["Complement Activation"]
G --> H["Inflammatory Response"]
I["VTN cleavage by MMPs"] --> J["VTN Fragments"]
J --> K["Synaptic Dysfunction"]
style A fill:#e1f5fe,stroke:#333
style C fill:#fff9c4,stroke:#333
style F fill:#e1f5fe,stroke:#333
style K fill:#ffcdd2,stroke:#333
- Vitronectin in Aβ pathology (Duong et al., 1999)
- VTN and microglial phagocytosis (Zhang et al., 2020)
- Vitronectin in brain physiology (Schvartz et al., 2019)
- VTN and neuroinflammation in AD (Yuan et al., 2021)
- VTN accumulation in brain plaques (Kosonen et al., 1997)
- VTN in synaptic plasticity (Victor et al., 2020)