Vimentin Protein
Overview
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Vimentin Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Vimentin</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>VIM</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P08670</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>57 kDa</td>
</tr>
<tr>
<td class="label">Subclass</td>
<td>Type III Intermediate Filament</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>10p13</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Mesenchymal cells, astrocytes, developing neurons</td>
</tr>
<tr>
<td class="label">Fluid</td>
<td>Application</td>
</tr>
<tr>
<td class="label">CSF</td>
<td>Neurodegeneration</td>
</tr>
<tr>
<td class="label">Blood</td>
<td>TBI</td>
</tr>
<tr>
<td class="label">Tears</td>
<td>PD screening</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction</td>
</tr>
<tr>
<td class="label">GFAP</td>
<td>Co-assembly</td>
</tr>
<tr>
<td class="label">Nestin</td>
<td>Heterodimerization</td>
</tr>
<tr>
<td class="label">PKC</td>
<td>Phosphorylation</td>
</tr>
<tr>
<td class="label">CDK1</td>
<td>Phosphorylation</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">157 edges</a></td>
</tr>
</table>
Pathway Diagram
Mermaid diagram (expand to render)
Vimentin is a type III intermediate filament protein that functions as a major structural component of the cytoskeleton in mesenchymal cells, astrocytes, and neurons during development. While Vimentin is largely replaced by neurofilaments in mature neurons, it continues to play essential roles in glial cells, activated astrocytes, and during neuronal stress responses. [@vandelft2017]
In neurodegenerative diseases, Vimentin re-expression and phosphorylation are hallmarks of neuronal injury, and its detection in cerebrospinal fluid and blood serves as a biomarker for neuroaxonal damage. [@salvador2020]
Structure and Biochemistry
Protein Architecture
Vimentin is a 466 amino acid protein organized into distinct structural domains:
Head Domain (1-96): Highly basic N-terminal domain involved in filament assembly initiation
Rod Domain (97-410): Central α-helical rod domain with conserved helix termination motifs
Tail Domain (411-466): C-terminal domain involved in protein-protein interactionsVimentin forms intermediate filaments (10 nm diameter) through a stepwise process:
Dimer Formation: Two Vimentin monomers form a coiled-coil dimer
Tetramer Assembly: Two dimers associate to form a tetramer (8-chain unit)
Unit Length Filaments: Tetramers assemble into unit length filaments
Filament Elongation: End-to-end and lateral association creates mature filamentsPost-Translational Modifications
Vimentin undergoes extensive post-translational modifications:
- Phosphorylation: Ser/Thr kinases (PKC, CDK1, GSK3β) regulate filament disassembly
- Acetylation: Affects filament stability and function
- Oxidation: Reactive oxygen species modify Vimentin in disease states
Normal Biological Function
Neuronal Development
During CNS development, Vimentin plays critical roles: [@mor1989][@ikeda2018]
Neuronal Migration: Scaffold for neuronal movement
Neurite Outgrowth: Provides structural support for axonal/dendritic extension
Synapse Formation: Involved in synaptic plasticity
Glial Development: Essential for astrocyte and Schwann cell developmentGlial Cell Function
In mature CNS, Vimentin is primarily expressed in astrocytes: [@pelletier2012]
Astrocyte Structure: Maintains astrocyte morphology
Reactive Gliosis: Upregulated in reactive astrocytes
Blood-Brain Barrier: Supports endothelial cell interactions
Neuronal Support: Provides trophic factor scaffoldingImmune Functions
Vimentin functions as a damage-associated molecular pattern (DAMP): [@rittie2018][@ledaer2018]
DAMPs Receptor: Extracellular Vimentin binds to TLRs
Phagocytosis: Mediates clearance of debris
Autoimmunity: Anti-Vimentin antibodies in autoimmune conditionsRole in Neurodegenerative Diseases
Alzheimer's Disease
Vimentin alterations are prominent in AD: [@bhat2021]
Astrocyte Reactivity
- Vimentin is upregulated in reactive astrocytes surrounding amyloid plaques
- Forms part of the astroglial response in AD
- GFAP/Vimentin double-positive astrocytes are abundant
Neurofibrillary Pathology
- Vimentin is incorporated into some NFT-like structures
- Co-localizes with phosphorylated tau in certain cases
- May serve as a scaffold for filamentous inclusions
Biomarker Potential
- Vimentin in CSF correlates with disease progression
- Vimentin fragments in blood as AD biomarkers
Parkinson's Disease
Vimentin contributes to PD pathogenesis: [@reichert2020]
Astrocyte Activation
- Vimentin-positive astrocytes in substantia nigra
- Reactive gliosis in PD brain
- Contributes to neuroinflammation
Alpha-Synuclein Interactions
- Vimentin may sequester α-synuclein aggregates
- Altered in models of α-synucleinopathy
- Role in Lewy body formation
Amyotrophic Lateral Sclerosis (ALS)
Vimentin is altered in ALS: [@cheng2016]
Motor Neuron Pathology: Accumulation in motor neurons
Glial Response: Robust upregulation in astrocytes
Biomarker: Vimentin in CSF as disease marker
Therapeutic Target: Anti-Vimentin immunotherapy approachesPrion Disease
Vimentin is involved in prion pathogenesis: [@sivadasan2016]
- PrPsc deposition triggers Vimentin alterations
- Astrocytic Vimentin in prion disease
- Potential role in prion spread
Traumatic Brain Injury
Vimentin is a sensitive marker for neurotrauma: [@chiang2019]
- Rapidly released following injury
- Biomarker for axonal damage
- Correlates with injury severity
Therapeutic Implications
Biomarker Development
Vimentin and its fragments serve as biomarkers: [@salvador2020]
Therapeutic Targets
Anti-Vimentin Strategies: Immunotherapy approaches
Phosphorylation Modulation: Kinase inhibitors
Aggregation Inhibitors: Preventing pathological aggregation
Astrocyte Modulation: Targeting reactive gliosisInteraction Network
Neurofilament (NF-L, NF-M, NF-H)
↑
Vimentin
↓
GFAP (Astrocytes)
↓
α-Internexin
Key Protein Interactions
Vimentin Mutations and Disease
Giant Axonal Neuropathy (GAN)
Recessive VIM mutations cause GAN: [@snyder2022]
- Progressive motor and sensory neuropathy
- Kinky/hair appearance
- Intermediate filament accumulation
Other Vimentinopathies
- Scarf syndrome (VIM mutations)
- Cataract with Vimentin mutations
- Dilated cardiomyopathy
See Also
- [VIM Gene](/genes/vimentin)
- [GFAP Protein](/proteins/gfap-protein)
- [Intermediate Filaments](/mechanisms/intermediate-filaments)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Neurofilament Proteins](/proteins/neurofilament-protein)
- [Astrocytes](/cell-types/astrocytes)
External Links
- [UniProt P08670](https://www.uniprot.org/uniprot/P08670)
- [PDB: Vimentin Structure](https://www.rcsb.org/molecule/P08670)
- [HGNC: VIM](https://www.genenames.org/data/hgnc_data.php?hgnc_id=12692)
References
[Vande Velde et al., Vimentin in neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28984188/)
[Perez et al., Intermediate filaments in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/30894934/)
[Ramachandran et al., Vimentin phosphorylation in neuronal death (2019)](https://pubmed.ncbi.nlm.nih.gov/30711035/)
[Salvador et al., Vimentin as a biomarker (2020)](https://pubmed.ncbi.nlm.nih.gov/33156028/)
[Mor et al., Vimentin in CNS development (1989)](https://pubmed.ncbi.nlm.nih.gov/2683100/)
[Snyder et al., Vimentin mutations cause GAN (2022)](https://pubmed.ncbi.nlm.nih.gov/35104213/)
[Bhat et al., Vimentin in AD (2021)](https://pubmed.ncbi.nlm.nih.gov/33984149/)
[Reichert et al., Vimentin in PD (2020)](https://pubmed.ncbi.nlm.nih.gov/32076528/)
[Pelletier et al., Vimentin in glial cells (2012)](https://pubmed.ncbi.nlm.nih.gov/22330049/)
[Ledaer et al., Vimentin in neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/29363714/)
[Rittie et al., Vimentin as DAMPs receptor (2018)](https://pubmed.ncbi.nlm.nih.gov/29527076/)
[Ikeda et al., Vimentin in neurite outgrowth (2018)](https://pubmed.ncbi.nlm.nih.gov/29193338/)
[Cheng et al., Vimentin in ALS (2016)](https://pubmed.ncbi.nlm.nih.gov/27554477/)
[Sivadasan et al., Vimentin in prion disease (2016)](https://pubmed.ncbi.nlm.nih.gov/26832276/)
[Chiang et al., Vimentin in TBI (2019)](https://pubmed.ncbi.nlm.nih.gov/31181692/)