Synaptotagmin 9 functions as a calcium ion receptor which regulates neurotransmitter vesicle release throughout the nervous system. Research demonstrates that Syt9 serves as a critical regulator of neuronal activity within specific central nervous system regions including the striatum which controls movement and reward processing.
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Synaptotagmin Family
Synaptotagmin family: Syt1, Syt2 and Syt9 function as primary calcium sensors which control the fusion and release of presynaptic vesicles.
Striate neurons: Intermediate spiny neurons (MSNs) make up the primary elements of the basal ganglia circuit.
Spontaneous neurotransmitter release: Neurons continue to release neurotransmitters at a low frequency without action potentials which supports synaptic plasticity and establishes baseline neural activity.
Expression and Function of Syt9 in Striatum
Syt9 expression dominates within striatal neurons and shows particular abundance in GABAergic neurons. Syt9 regulates spontaneous transmitter release while Syt1 controls action potential-dependent evoked release. The elimination of Syt9 expression caused a substantial decrease in the appearance rate of vagal bodies.
Potential Mechanisms
Calcium ion-sensitive mechanism
Syt9 demonstrates lower calcium sensitivity which makes it ideal for detecting weaker calcium signals to maintain spontaneous release control.
Vesicle type selectivity
A particular vesicle subclass that controls spontaneous release could be targeted by Syt9 binding.
Interaction with other proteins
The protein Syt9 interacts with SNARE complex proteins including syntaxin-1 and VAMP2 to control vesicle fusion probability.
Expression of Syt-9 in Pituitary and Other Brain Regions
Synaptotagmin-9 belongs to the synaptotagmin family and is a Ca2+ receptor that is primarily involved in regulating the release of neurotransmitters and hormones. The expression of Syt9 is brain region specific.
Overview of Expression Regions
| Brain regions/tissues |
Expression level |
Physiological function relevance |
| Pituitary gland |
Moderate to high |
Involved in hormone vesicle release, such as gonadotropin, prolactin. |
| Striatum |
High expression |
Regulates the spontaneous release of GABA and glutamate |
| Hippocampus |
Detectable |
Involved in synaptic plasticity and learning and memory |
| Hypothalamus |
Moderate |
Related to energy metabolism and endocrine regulation |
| Prefrontal cortex |
Low to moderate |
Or related to emotional regulation and cognitive function |
Functional Speculation in Pituitary
- The anterior pituitary mainly releases a variety of peptide hormones (such as ACTH and GH).
- Syt9 may act as a Ca2+ receptor in the pituitary, mediating the fusion and release of hormone vesicles.
- It is co-expressed with Syt1 and Syt7, and may have complementary or phased division of labor.
Syt-9 Folds t-SNARE to Drive Ca2+ -Regulated Membrane Fusion
Introduction to SNARE Complex Mechanism
- t-SNARE (target-SNARE): Syntaxin-1 and SNAP-25 represent proteins situated within the plasma membrane.
- v-SNARE (vesicle-SNARE): The protein VAMP2 serves as an example of a vesicle-SNARE located within the vesicle membrane.
- Membrane fusion receives its driving energy from the SNARE complex folding process.
Differences between Syt9 and Syt1
| Characteristics |
Syt1 |
Syt9 |
| Expression region |
Widely (cerebral cortex, hippocampus) |
Striata, pituitary |
| Ca2+ sensitivity |
High |
Moderate to low |
| Release type |
Fast evoked release |
Spontaneous release + hormone vesicle release |
| SNARE mode of action |
Tightly binds to SNARE |
More inclined to regulate the SNAP-25 folding step |
Syt9 Physiological and Pathological Significance
- Neural circuit development: Synapse formation and fine regulation depend on spontaneous release which Syt9 influences in striatal development.
- Relevance to mental illness: Dysfunction in the striatum leads to depression and Parkinson's disease as well as schizophrenia and additional disorders. Certain pathological conditions show synaptic transmission disorders that may arise from abnormal Syt9 function.
The protein Syt9 shows high expression levels in both the pituitary and striatum while controlling the release processes of neurotransmitters along with peptide hormones. The primary "trigger" function of Syt9 in calcium-dependent membrane fusion involves the regulation of t-SNARE folding states essential for spontaneous and slow release systems.
References
- Zhang, M., et al. The cytidine N-acetyltransferase NAT10 participates in peripheral nerve injury-induced neuropathic pain by stabilizing SYT9 expression in primary sensory neurons. Journal of Neuroscience. 2023, 43(17): 3009-3027.
- Seibert, Mi., et al. Synaptotagmin 9 modulates spontaneous neurotransmitter release in striatal neurons by regulating substance P secretion. Journal of Neuroscience. 2023, 43(9): 1475-1491.
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