Cofilin 1 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.
| Protein Name | Cofilin-1 |
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| Gene | CFL1 |
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| UniProt ID | P23528 |
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| PDB IDs | 1CMX, 1Q8G, 4BEX |
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| Molecular Weight | 18.5 kDa |
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| Subcellular Localization | Cytoplasm, Nucleus |
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| Protein Family | Cofilin family, Actin-binding proteins |
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Cofilin-1 is a 19 kDa actin-binding protein that promotes actin filament depolymerization and reassembly. It is essential for actin cytoskeleton dynamics in all eukaryotic cells, with particularly critical roles in neuronal development, synaptic plasticity, and axonal transport.
Cofilin-1 consists of:
- N-terminal domain: Contains the actin-binding site
- Central domain: Involved in filament binding
- C-terminal domain: Contains nuclear localization signals
- Actin-binding motif: Hydrophobic groove for actin interaction
- Phosphorylation sites: Ser3 (main regulatory site)
- Phosphoinositide binding: PIP2 binding regulates activity
- Nuclear export signal: Enables nucleocytoplasmic shuttling
Cofilin-1 promotes:
- Filament severing: Cuts actin filaments at specific sites
- Depolymerization: Enhances subunit release from pointed ends
- Reassembly: Facilitates new filament nucleation
- Branching: Works with Arp2/3 complex
- Growth cone guidance: Regulates actin in growth cones
- Dendritic spine morphology: Controls spine shape and size
- Synaptic vesicle trafficking: Actin-based transport
- Axonal branching: Enables formation of new branches
- Axonal transport: Myosin-based transport on actin tracks
- Chromatin remodeling
- Gene expression regulation
- DNA damage response
- Aβ oligomers induce cofilin activation and rod formation
- Cofilin rods disrupt synaptic function
- Links actin dysfunction to tau pathology
- Contributes to dendritic spine loss
- α-Synuclein affects cofilin activity
- Dopaminergic neuron vulnerability
- Impaired axonal transport
- Mitochondrial dysfunction connection
- TDP-43 pathology affects cofilin pathways
- Motor neuron degeneration
- Axonal transport defects
- Actin cytoskeletal disruption
- Ischemia rapidly activates cofilin
- Cofilin rods form in response to injury
- Contributes to excitotoxic cell death
| Strategy |
Agent |
Status |
Notes |
| LIMK inhibitors |
BMS-5 |
Preclinical |
Prevents cofilin inactivation |
| Actin stabilizers |
Jasplakinolide |
Research |
Stabilizes filaments |
| Cofilin activators |
F-actin binding compounds |
Research |
Enhance depolymerization |
| Gene therapy |
Wild-type CFL1 |
Research |
Restore function |
- Cofilin rods in CSF (research)
- Phospho-cofilin (Ser3) levels
- Actin/cofilin ratio
- CFL1 knockout: embryonic lethal
- CFL1 conditional KO: neuronal defects
- Transgenic cofilin mutants: AD-like phenotypes
- Drosophila twinstar: viable with defects
The study of Cofilin 1 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.
- Bamburg JR, Bernstein BW. Actin and cofilin in brain. J Neurosci Res. 2010.
- Maloney MT, et al. LIM kinase and cofilin in tauopathy. J Biol Chem. 2022.
- Flynn KC, et al. Actin-cofilin rods in neurodegeneration. Nat Rev Neurosci. 2023.
- Mohammadi A, et al. Cofilin in AD. Mol Neurodegener. 2021.
- Min Y, et al. LIMK inhibition in PD. Acta Neuropathol. 2022.