SYT4
Synaptotagmin 4
| Property |
Value |
| Chromosomal Location |
18q12.3 |
| NCBI Gene ID |
6860 |
| UniProt |
Q9H0Y5 |
| Ensembl ID |
ENSG00000124614 |
| Associated Diseases |
Epilepsy, autism spectrum disorders, neurodegenerative diseases, schizophrenia |
SYT4 (Synaptotagmin 4) is a member of the synaptotagmin family of calcium-binding proteins that regulate neurotransmitter release at synapses [1]. Unlike most synaptotagmins, SYT4 functions as a calcium-independent regulator and is primarily involved in modulating synaptic plasticity rather than triggering fast exocytosis.
SYT4 is located on chromosome 18q12.3 and encodes a protein with:
- N-terminal signal peptide
- C2A domain: Calcium-binding (but with low affinity)
- C2B domain: Protein-protein interactions
- Transmembrane anchor: C-terminal transmembrane region
Synaptotagmins are calcium sensors for synaptic vesicle exocytosis:
- Two C2 domains bind calcium with varying affinities
- Rapid calcium detection (<1 millisecond)
- Trigger vesicle fusion (for fast-synaptotagmins)
Unlike SYT1/SYT2 (fast calcium sensors), SYT4 has unique properties [2]:
- Calcium-independent activity: Functions as a dominant-negative regulator
- Vesicle replenishment: Regulates synaptic vesicle pool size
- Plasticity modulation: Affects short-term plasticity (depression/facilitation)
- Asynchronous release: Influences asynchronous neurotransmitter release
- SNARE complex: Binds to SNARE proteins (SNAP-25, VAMP)
- Complexin: Modulates interaction with complexin
- Synaptotagmin-1: Can antagonize SYT1 function
- Neuronal calcium sensors: Interacts with recoverin family proteins
SYT4 is expressed in:
- Brain: Hippocampus (CA3, dentate gyrus), cortex, cerebellum, basal ganglia
- Specific populations: GABAergic interneurons, certain pyramidal neurons
- Development: Higher expression during development, declines in adulthood
- Peripheral tissue: Some expression in endocrine cells
- SYT4 dysregulation in epileptic tissue
- Alters seizure threshold and plasticity
- May affect inhibitory neurotransmission
- SYT4 mutations associated with ASD
- Impacts synaptic development and function
- Related to social and cognitive phenotypes
- SYT4 expression altered in schizophrenic brains
- Potential role in synaptic pruning abnormalities
- SYT4 modulators: Potential for treating epilepsy or ASD
- Synaptic stabilizers: Targeting SYT4 function may protect synapses
- Gene therapy: Restore SYT4 expression levels
- SYT4 as a marker for specific neuronal populations
- Fluorescent reporters for SYT4 localization
- Syt4 knockout mice: Viable with subtle behavioral phenotypes
- Transgenic overexpression: Alters plasticity and learning
- Zebrafish: SYT4 morphants show developmental defects
| Synaptotagmin |
Calcium Sensor |
Primary Function |
| SYT1 |
Yes (high affinity) |
Fast synchronous release |
| SYT2 |
Yes (high affinity) |
Fast synchronous release |
| SYT4 |
Low/no |
Plasticity modulation |
| SYT7 |
Yes (low affinity) |
Asynchronous release, vesicle replenishment |
| SYT9 |
Yes |
Various |