FZD3 Protein

FZD3 Protein - Frizzled-3 Receptor

Introduction

Fzd3 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.

<div class="infobox infobox-protein"> [@wang2021]
<table> [@mukai2022]
<tr><th colspan="2" class="infobox-header">FZD3 Protein</th></tr>
<tr><th colspan="2" class="infobox-subheader">Frizzled Class Receptor 3</th></tr>
<tr><td class="label">Gene</td><td>[FZD3](/genes/fzd3)</td></tr>
<tr><td class="label">UniProt ID</td><td>Q9UPW4</td></tr>
<tr><td class="label">PDB ID</td><td>6MQJ</td></tr>
<tr><td class="label">Molecular Weight</td><td>64,500 Da</td></tr>
<tr><td class="label">Subcellular Localization</td><td>Plasma membrane</td></tr>
<tr><td class="label">Protein Family</td><td>Frizzled receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>
</div>

Overview

FZD3 (Frizzled-3) is a seven-transmembrane receptor protein that functions as the primary receptor for non-canonical Wnt signaling, particularly the planar cell polarity (PCP) pathway. It plays critical roles in neuronal migration, axon guidance, and synaptic formation during development and in adult brain function.

Structure

Transmembrane Domain

FZD3 Protein - Frizzled-3 Receptor

Introduction

Fzd3 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.

<div class="infobox infobox-protein"> [@wang2021]
<table> [@mukai2022]
<tr><th colspan="2" class="infobox-header">FZD3 Protein</th></tr>
<tr><th colspan="2" class="infobox-subheader">Frizzled Class Receptor 3</th></tr>
<tr><td class="label">Gene</td><td>[FZD3](/genes/fzd3)</td></tr>
<tr><td class="label">UniProt ID</td><td>Q9UPW4</td></tr>
<tr><td class="label">PDB ID</td><td>6MQJ</td></tr>
<tr><td class="label">Molecular Weight</td><td>64,500 Da</td></tr>
<tr><td class="label">Subcellular Localization</td><td>Plasma membrane</td></tr>
<tr><td class="label">Protein Family</td><td>Frizzled receptor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>
</div>

Overview

FZD3 (Frizzled-3) is a seven-transmembrane receptor protein that functions as the primary receptor for non-canonical Wnt signaling, particularly the planar cell polarity (PCP) pathway. It plays critical roles in neuronal migration, axon guidance, and synaptic formation during development and in adult brain function.

Structure

Transmembrane Domain

FZD3 contains seven transmembrane α-helices typical of G-protein-coupled receptors:

• N-terminal extracellular cysteine-rich domain (CRD) for Wnt ligand binding
• Three extracellular loops
• Three intracellular loops
• C-terminal intracellular tail with PDZ-binding motif

Crystal Structure

The CRD domain of FZD3 has been solved (PDB: 6MQJ), revealing:

• Wnt ligand binding interface
• Dimerization interface
• Conservation of key binding residues

Normal Function

Non-Canonical Wnt Signaling

FZD3 primarily mediates non-canonical Wnt signaling:

• Activates Wnt/PCP pathway via DVL recruitment
• Modulates cytoskeletal dynamics through small GTPases
• Regulates cell polarity and migration
• Controls axonal tract formation

Neural Development

In the developing nervous system:

• Cortical neuron migration via radial glia
• Axon guidance in corpus callosum formation
• Cerebellar granule cell migration
• Dendritic morphogenesis

Synaptic Function

In mature [neurons](/entities/neurons):

• Regulates synapse formation and maintenance
• Modulates dendritic spine morphology
• Controls neurotransmitter release
• Influences plasticity mechanisms

Role in Disease

Alzheimer's Disease

FZD3 dysregulation contributes to AD:

• Altered Wnt/PCP signaling in AD brains
• Deficiency exacerbates cognitive deficits
• Protective role against [Aβ](/proteins/amyloid-beta) toxicity
• Therapeutic potential of FZD3 activation

Neuropsychiatric Disorders

FZD3 associations with:

• Schizophrenia
• Autism spectrum disorders
• Bipolar disorder

Neurodevelopmental Disorders

Mutations cause:

• Brain malformations
• Cognitive impairment

Therapeutic Targeting

Small Molecule Agonists

Wnt pathway activators that target FZD3:

• Wnt agonists restoring PCP signaling
• FZD3-selective compounds

Antibody Therapies

FZD3-specific antibodies:

• Targeting FZD3 for research
• Potential therapeutic applications

Gene Therapy

Viral vector delivery of FZD3:

• Restoring Wnt signaling
• Protecting against neurodegeneration

Key Publications

Interactions

FZD3 interacts with:

• WNT1, WNT3A, WNT5A, WNT11: Wnt ligands
• DVL1, DVL2, DVL3: Dishevelled proteins
• VANGL1, VANGL2: PCP core components
• CELSR1, CELSR2: Cadherin receptors
• LRP5, LRP6: Co-receptors

See Also

• [FZD3 Gene](/genes/fzd3)
• [Wnt Signaling Pathway](/mechanisms/wnt-signaling-neurodegeneration)
• [Planar Cell Polarity](/mechanisms/planar-cell-polarity-neurodegeneration)
• [Alzheimer's Disease](/diseases/alzheimers-disease)

Background

The study of Fzd3 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.

External Links

• [UniProt: FZD3](https://www.uniprot.org/uniprot/Q9UPW4)
• [PDB: 6MQJ](https://www.rcsb.org/structure/6MQJ)
• [NCBI Gene: FZD3](https://www.ncbi.nlm.nih.gov/gene/7976)

References