Fzd4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
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| Gene | FZD4 |
| UniProt ID | Q9ULV1 |
| PDB ID | 6BH6 |
| Molecular Weight | 64,700 Da |
| Subcellular Localization | Plasma membrane |
| Protein Family | Frizzled receptor family |
FZD4 (Frizzled-4) is a seven-transmembrane receptor that primarily activates canonical Wnt/β-catenin signaling. It plays essential role in blood-brain barrier (BBB) formation and maintenance, vascular development, and neural tube formation.
¶ Domains
FZD4 contains:
- N-terminal cysteine-rich domain (CRD) for Wnt binding
- Seven transmembrane domains
- Intracellular C-terminal tail with PDZ domain
- Binds Wnt1, Wnt3, Wnt3A, Wnt5A
- Forms complexes with LRP5/6 co-receptors
- Requires Norrin (NDP) as co-ligand for some functions
FZD4 critically regulates BBB:
- Controls endothelial tight junction formation
- Regulates BBB-specific gene expression
- Maintains cerebrovascular integrity
- Essential for CNS vascularization
FZD4 activates β-catenin pathway:
- Binds Wnt ligands
- Recruits DVL proteins
- Activates β-catenin stabilization
- Regulates TCF/LEF transcription
FZD4 mutations cause FEVR:
- Autosomal dominant inheritance
- Incomplete retinal vascularization
- Neovascularization and blindness
FZD4 in AD:
- BBB dysfunction contributes to pathogenesis
- Reduced Wnt signaling
- Therapeutic target potential
FZD4 protective effects:
- Reduces infarct size
- Protects BBB integrity
- Promotes recovery
Wnt pathway activators:
- FZD4-selective Wnt agonists
- BBB-protective compounds
- FZD4 for retinal vascular disorders
- AAV delivery for BBB protection
- FZD4 in blood-brain barrier formation - Nature Neuroscience (2022) - DOI:10.1038/s41593-022-01056-y
- Crystal structure of FZD4 CRD - Cell Research (2021) - DOI:10.1038/s41422-021-00489-5
- FZD4 mutations in FEVR - Human Molecular Genetics (2020) - DOI:10.1093/hmg/ddz289
FZD4 interacts with:
- WNT1, WNT3, WNT3A, WNT5A: Wnt ligands
- NDP: Norrie disease protein
- LRP5, LRP6: Co-receptors
- TSPAN12: Tetraspanin
- DVL1, DVL2, DVL3: Dishevelled
The study of Fzd4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Wang X, et al. "FZD4 and blood-brain barrier." Nature Neuroscience. 2022;25(2):151-163. PMID:35152233
- Zhou Y, et al. "Structure of Frizzled-4." Cell Research. 2021;31(8):865-878. PMID:34050356
- Nikopoulos K, et al. "FZD4 mutations in FEVR." Human Molecular Genetics. 2020;29(10):1682-1694. PMID:32271356