Cortactin (CTTN) is an actin-binding protein that promotes actin polymerization and branching. It plays critical roles in cytoskeletal dynamics, cell motility, and synaptic function. Dysregulation of cortactin is implicated in several neurodegenerative diseases.
Cortactin is a ~80 kDa protein containing:
- N-terminal acidic (NTA) region: Binds Arp2/3 complex
- 6.5 repeats of cortactin repeat domain (CTD): F-actin binding
- Helical domain: Protein-protein interactions
- C-terminal SH3 domain: Binds proline-rich motifs in binding partners
The protein is tyrosine-phosphorylated in response to various stimuli, modulating its activity.
- Actin Polymerization: Activates Arp2/3 complex to initiate new actin branches
- Cytoskeletal Organization: Stabilizes actin networks
- Cell Motility: Promotes lamellipodia and filopodia formation
- Endocytosis: Regulates vesicle trafficking
- Synaptic Function: Controls dendritic spine morphology and synaptic plasticity
- Hyperphosphorylated tau affects cortactin function
- Altered synaptic spine morphology
- Dysregulated actin dynamics in early AD
- Alpha-synuclein aggregation disrupts cortactin-mediated trafficking
- Impaired dopaminergic neuron connectivity
- Altered endocytic pathways
- Mutations in cortactin (CTTN) identified in some ALS cases
- Dysregulated actin cytoskeleton in motor neurons
- Impaired axonal transport
- Altered synaptic spine formation and maintenance
- Impaired axonal transport due to cytoskeletal defects
- Dysregulated endocytosis affecting protein clearance
- Targeting actin cytoskeleton regulators
- Enhancing synaptic plasticity through cortactin modulation
- Improving axonal transport
- Arp2/3 Complex: Direct activation of actin branching
- F-actin: Binding and stabilization
- Shank proteins: Synaptic scaffolding
- Rho GTPases: Regulation of cortactin phosphorylation
- NMDA Receptor: Synaptic signaling modulation
Additional evidence sources: