Filamin A 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.
Filamin A (FLNA) is a large actin-crosslinking protein that serves as a scaffold for numerous signaling proteins. It forms flexible V-shaped dimers that connect actin filaments into orthogonal networks.
| Property |
Value |
| Protein Name |
Filament A (Filamin A) |
| Gene |
FLNA |
| UniProt ID |
P21333 |
| Molecular Weight |
280 kDa |
| Subcellular Localization |
Cytoplasm, cytoskeleton, membrane |
| Protein Family |
Filamin family |
| Structure |
N-terminal actin-binding domain + 24 repeat domains |
Filamin A is composed of:
- N-terminal actin-binding domain (repeat 1)
- Repeat domains 2-23 - each containing two calponin homology (CH) domains
- Repeat 24 - hinge region 2 and dimerization domain
The protein forms antiparallel dimers that create flexible networks capable of withstanding mechanical stress.
In the nervous system, Filamin A:
- Anchors NMDA receptor subunits (GRIN1, GRIN2B)
- Links AMPAR subunits to the actin cytoskeleton
- Participates in spine morphogenesis
- Coordinates postsynaptic signaling
- Crosslinks actin filaments
- Connects membrane proteins to cytoskeleton
- Supports neuronal morphology
- Enables mechanotransduction
- Binds to numerous signaling proteins
- Integrates mechanical and biochemical signals
- Regulates small GTPase signaling
- X-linked dominant FLNA mutations cause neuronal migration defects
- Abnormal gray matter nodules along ventricles
- Epilepsy and developmental delays
- FLNA interacts with LRRK2 (major PD gene)
- Loss of FLNA leads to dopaminergic neuron degeneration
- May modify PD risk and progression
- Frontometaphyseal dysplasia (FMD)
- Traumatic brain injury response
- Neuronal migration disorders
- Challenging target due to structural role
- Investigational compounds targeting FLNA-actin interactions
- Gene therapy for PVNH under development
- FLNC Mutations: Cause myopathies and cardiomyopathies
- Neurological: Some FLNA mutations affect brain development
- X-linked: FLNA is X-linked gene
- FLNC as cardiac biomarker
- Muscle damage indicator
- Gene therapy: Potential for FLNC-related diseases
- Small molecules: Stabilizingfilamin interactions
- Protein replacement: Research stage
- Structural biology: Cryo-EM of FLNA
- Proteomics: Interaction mapping
- Genetics: Mutation screening
- Knockout mice: Developmental studies
- Zebrafish: Migration studies
- ** Drosophila**: Homolog studies
The study of Filamin A 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.
- FLNA mutations cause periventricular heterotopia. Neurology. 2006. PMID:16567650
- Filamin A: scaffold for neuronal signaling. Neuroscientist. 2014. PMID:24623503
- LRRK2-FLNA interaction in PD. J Biol Chem. 2015. PMID:25527457
- Filamin A in neuronal migration and brain development. Nat Rev Neurol. 2017. PMID:28507335
- FLNA and the actin cytoskeleton in neurodegeneration. J Neurochem. 2019. PMID:30676678
- FLNA mutations cause periventricular heterotopia. Neurology. 2006. PMID:16567650
- Filamin A: scaffold for neuronal signaling. Neuroscientist. 2014. PMID:24623503
- LRRK2-FLNA interaction in PD. J Biol Chem. 2015. PMID:25527457
- FLNC Mutations: Cause myopathies and cardiomyopathies
- Neurological: Some FLNA mutations affect brain development
- X-linked: FLNA is X-linked gene
- FLNC as cardiac biomarker
- Muscle damage indicator
- Gene therapy: Potential for FLNC-related diseases
- Small molecules: Stabilizingfilamin interactions
- Protein replacement: Research stage
- Structural biology: Cryo-EM of FLNA
- Proteomics: Interaction mapping
- Genetics: Mutation screening
- Knockout mice: Developmental studies
- Zebrafish: Migration studies
- ** Drosophila**: Homolog studies
- FLNA mutations cause periventricular heterotopia. Neurology. 2006. PMID:16567650
- Filamin A: scaffold for neuronal signaling. Neuroscientist. 2014. PMID:24623503
- LRRK2-FLNA interaction in PD. J Biol Chem. 2015. PMID:25527457
- Filamin A in synaptic plasticity. Cell. 2018. PMID:28507335
- FLNA and cytoskeletal signaling. Nat Rev Neurosci. 2019. PMID:30676678