Septin 4

Septin 4

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Septin 4</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>| [@septinb]</td>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SEPTIN4</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Septin 4</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q23.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[SEPTIN4](https://www.ncbi.nlm.nih.gov/gene/)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[O43291](https://www.uniprot.org/uniprot/O43291)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Parkinson's Disease, Multiple System Atrophy, Cancer</td>
</tr>
</table>

Septin 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

.infobox .infobox-gene [@septina]

Overview

Septin 4

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">Septin 4</th>
</tr>
<tr>
<td class="label">Gene</td>
<td>| [@septinb]</td>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SEPTIN4</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Septin 4</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>17q23.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[SEPTIN4](https://www.ncbi.nlm.nih.gov/gene/)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[O43291](https://www.uniprot.org/uniprot/O43291)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Parkinson's Disease, Multiple System Atrophy, Cancer</td>
</tr>
</table>

Septin 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

.infobox .infobox-gene [@septina]

Overview

SEPTIN4 (Septin 4) is a member of the septin family of GTP-binding proteins that play essential roles in cytoskeletal organization, membrane dynamics, and cell division. In the nervous system, SEPTIN4 has attracted particular attention due to its involvement in neurodegenerative diseases, especially Parkinson's disease (PD) and Multiple System Atrophy (MSA). SEPTIN4 is a component of Lewy bodies and other protein aggregates characteristic of synucleinopathies, suggesting important roles in protein aggregation pathways and neuronal vulnerability.

Molecular Mechanism

SEPTIN4 belongs to the septin family, which comprises GTP-binding proteins that form heterooligomeric complexes and filaments. Unlike traditional GTPases, septins function as scaffold proteins that organize membrane microdomains and cytoskeletal structures.

GTP Binding and Hydrolysis

SEPTIN4, like other septins, binds GTP and can hydrolyze it to GDP, though the GTPase activity is relatively slow compared to classical GTPases. The GTP-bound and GDP-bound states have different conformations, allowing SEPTIN4 to act as a molecular switch.

Filament Formation

SEPTIN4 forms higher-order structures:

• Hetero-oligomeric complexes: SEPTIN4 assembles with other septins (SEPT1, SEPT2, SEPT3, SEPT5, SEPT6, SEPT7, SEPT8, SEPT9, SEPT10, SEPT11, SEPT12, SEPT14) into complexes
• Filaments and bundles: These complexes can polymerize into filaments and higher-order bundles
• Membrane association: SEPTIN4 localizes to membrane compartments, particularly Golgi and plasma membrane

Protein-Protein Interactions

SEPTIN4 interacts with numerous proteins relevant to neurodegeneration:

• [Alpha-synuclein](/proteins/alpha-synuclein): SEPTIN4 colocalizes with α-syn in Lewy bodies
• Parkin: Interactions with E3 ubiquitin ligase parkin
• Tubulin: SEPTIN4 can associate with microtubules
• Synaptic proteins: Involvement in synaptic vesicle trafficking

Subcellular Localization

SEPTIN4 exhibits distinctive subcellular distribution:

• Cytosol: Diffuse cytoplasmic pool
• Membrane compartments: Golgi apparatus, plasma membrane
• Neuronal processes: Axons and dendrites
• Synaptic terminals: Presynaptic and postsynaptic compartments
• Aggregate localization: Present in Lewy bodies and glial cytoplasmic inclusions

Disease Associations

Parkinson's Disease

SEPTIN4 has emerged as an important player in Parkinson's disease:

Multiple System Atrophy

In MSA, SEPTIN4 is found in:

Cancer

SEPTIN4 has been studied in cancer biology:

Therapeutic Implications

SEPTIN4 represents a potential therapeutic target:

Modulation Strategies

• Septin filament stabilizers: Compounds promoting proper septin assembly
• Aggregation pathway modulators: Targeting SEPTIN4-α-syn interactions
• Gene therapy approaches: Modulating SEPTIN4 expression

Biomarker Potential

• CSF SEPTIN4: Potential biomarker for synucleinopathies
• Peripheral measurements: SEPTIN4 in blood or other tissues

Research Directions

Key questions include:

Key Publications

Background

The study of Septin 4 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.

See Also

• [Genes Index](/genes)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy)
• [Lewy Body Dementia](/diseases/lewy-body-dementia)
• [Alpha-Synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-pathology)
• [Protein Quality Control](/mechanisms/protein-quality-control-network)

External Links

• [NCBI Gene: SEPTIN4](https://www.ncbi.nlm.nih.gov/gene/)
• [UniProt: O43291](https://www.uniprot.org/uniprot/O43291)

References