Tenascin-C (TNC) is a large hexameric extracellular matrix (ECM) glycoprotein expressed during embryonic development and re-expressed in various pathological conditions including wound healing, inflammation, and cancer. In the nervous system, Tenascin-C plays important roles in neural development, synaptic plasticity, and regenerative responses following injury. It is also implicated in the pathogenesis of neurodegenerative diseases and gliomas.
:: infobox .infobox-protein
| Tenascin-C Protein |
|
| Gene |
TNC (no dedicated gene page) |
| UniProt |
P24821 |
| Molecular Weight |
~190-220 kDa (subunit), ~1,000 kDa (hexamer) |
| Subcellular Localization |
Extracellular matrix |
| Protein Family |
Tenascin family |
| Aliases |
Tenascin-C, TNC, Cytotactin, Hexabrachion |
===
¶ Domain Architecture
Tenascin-C is a large, multifunctional glycoprotein with a complex structure:
- N-terminal heptad domain: Mediates hexamer formation (6 subunits)
- Epidermal growth factor (EGF)-like repeats: 13.5 repeats (14-15 total)
- Fibronectin type III (FNIII) repeats: 15 repeats (variable splicing)
- C-terminal fibrinogen globe (FBG): Mediates protein-protein interactions
Tenascin-C undergoes extensive alternative splicing:
- Inclusion/exclusion of FNIII repeats: Creates isoforms with different binding properties
- Variable expression: Different isoforms in development vs. adult tissue
- Functional implications: Isoform-specific interactions with integrins and other ECM proteins
- Forms a hexameric "hexabrachion" structure
- Six subunits connected at the N-terminal termini
- Creates a star-like appearance under electron microscopy
Tenascin-C is highly expressed during embryonic development:
- Axon guidance: Provides guidance cues for growing axons
- Cell adhesion: Mediates neuronal-glial interactions
- Neural crest cell migration: Important for neural crest derivation
- Cortical development: Regulates neuronal positioning
In the mature nervous system:
- Synaptic plasticity: Modulates synaptic strength and structure
- Hippocampal function: Involved in learning and memory
- Neuromuscular junction: Regulates postsynaptic specializations
- Astrocyte function: Promotes astrocyte migration and process extension
- Oligodendrocyte development: Supports myelination
- Schwann cell function: Peripheral nerve regeneration
Tenascin-C is highly expressed in gliomas:
- Tumor progression: Promotes invasion and angiogenesis
- Biomarker: Potential diagnostic and prognostic marker
- Therapeutic target: Antibody-based therapies in development
- Re-expressed in AD brains
- Co-localizes with amyloid plaques
- May influence plaque formation or glial response
- Expressed in demyelinating lesions
- Promotes glial scarring
- May inhibit remyelination
- Up-regulated after injury
- Dual role: promotes regeneration vs. forms glial scar
- Target for regenerative therapies
| Approach |
Description |
Status |
| Anti-tenascin antibodies |
Tumor-targeted therapy |
Clinical trials |
| Peptide antagonists |
Block tenascin-integrin interactions |
Research |
| Gene therapy |
Modulate tenascin-C expression |
Preclinical |
Tenascin-C interacts with:
- Integrins: α8β1, αvβ3, α9β1, αvβ6
- Fibronectin: ECM network formation
- Heparin/heparan sulfate: ECM binding
- NG2 proteoglycan: Pericyte interactions