regulation of synaptic vesicle fusion to presynaptic active zone membrane
Definition
Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of synaptic vesicle fusion to the presynaptic membrane. [GOC:mah]
The regulation of synaptic vesicle fusion to the presynaptic active zone membrane is a complex and tightly controlled process that underlies neurotransmission. It involves a cascade of molecular events, beginning with the arrival of an action potential at the presynaptic terminal. This triggers a series of events that ultimately lead to the release of neurotransmitters into the synaptic cleft.
**1. Calcium Influx:** The action potential depolarizes the presynaptic membrane, opening voltage-gated calcium channels (primarily Cav2.1 channels). Calcium ions (Ca2+) rapidly influx into the presynaptic terminal, triggering the fusion process.
**2. SNARE Complex Assembly:** The influx of Ca2+ activates a protein complex known as the Soluble NSF Attachment Protein Receptor (SNARE) complex. This complex comprises proteins located on both the synaptic vesicle (v-SNAREs: synaptobrevin) and the plasma membrane of the presynaptic terminal (t-SNAREs: syntaxin and SNAP-25).
- Synaptobrevin binds to SNAP-25 and syntaxin, initiating the formation of a four-helix bundle, bringing the vesicle membrane close to the plasma membrane.
**3. Synaptotagmin: The Calcium Sensor:** Synaptotagmin, a calcium-binding protein, interacts with the SNARE complex and acts as the primary calcium sensor.
- Upon calcium binding, synaptotagmin undergoes a conformational change, triggering a series of events that ultimately promote vesicle fusion.
**4. Vesicle Fusion and Neurotransmitter Release:** Synaptotagmin interacts with the SNARE complex and promotes vesicle fusion with the plasma membrane. This results in the release of neurotransmitter molecules into the synaptic cleft.
**5. Vesicle Recycling:** After fusion, the synaptic vesicle membrane is retrieved from the plasma membrane through a process called endocytosis. This involves the formation of clathrin-coated pits and the subsequent reformation of new synaptic vesicles. These recycled vesicles are then primed for another round of neurotransmitter release.
**Regulation and Fine-Tuning:**
- **Calcium Concentration:** The amount of calcium influx directly influences the rate of vesicle fusion. Higher calcium levels promote faster and more frequent vesicle fusion, leading to increased neurotransmitter release.
- **Synaptic Plasticity:** The regulation of synaptic vesicle fusion is also subject to long-term changes, contributing to synaptic plasticity. This includes processes like long-term potentiation (LTP) and long-term depression (LTD), which modify the strength of synaptic connections in the brain.
**Key Proteins Involved in Vesicle Fusion:**
- **SNARE Proteins:** Synaptobrevin (v-SNARE), Syntaxin and SNAP-25 (t-SNAREs)
- **Synaptotagmin:** Calcium sensor and fusion mediator
- **Complexins:** Regulate SNARE complex assembly and stability
- **Munc13:** Promotes SNARE complex assembly and priming of vesicles
- **NSF:** ATPase that disassembles the SNARE complex after fusion
- **α-SNAP:** Facilitates SNARE complex disassembly
**Conclusion:** The regulation of synaptic vesicle fusion is a fundamental process in neuronal communication. It involves a delicate interplay of proteins and calcium signaling, ensuring the efficient and precise release of neurotransmitters at the synapse. Understanding this process is critical for elucidating the molecular basis of brain function and for developing therapeutic strategies for neurological disorders.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Glutamate receptor ionotropic, kainate 5 | A glutamate receptor ionotropic, kainate 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16478] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid | alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies. | non-proteinogenic alpha-amino acid | |
| kainic acid | Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. | dicarboxylic acid; L-proline derivative; non-proteinogenic L-alpha-amino acid; pyrrolidinecarboxylic acid | antinematodal drug; excitatory amino acid agonist |
| glutamic acid | glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2. Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM. | glutamic acid; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid | Escherichia coli metabolite; ferroptosis inducer; micronutrient; mouse metabolite; neurotransmitter; nutraceutical |
| 5-fluorowillardiine | 3-(5-fluorouracil-1-yl)-L-alanine : An alanine derivative that is L-alanine bearing a 5-fluorouracil-1-yl substituent at position 3. A more potent and selective AMPA receptor agonist (at hGluR1 and hGluR2) than AMPA itself (Ki = 14.7, 25.1, and 1820 nM for hGluR1, hGluR2 and hGluR5 respectively). 5-fluorowillardiine: a glutamate agonist; RN given for (S)-isomer | L-alanine derivative; non-proteinogenic L-alpha-amino acid; organofluorine compound | AMPA receptor agonist |
| ly 293558 | tezampanel: structure given in first source; an AMPA receptor antagonist | ||
| alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid | |||
| 5-bromowillardiine | 5-bromowillardiine: acts as a kainate-like agonist on chick EAA receptors expressed in Xenopus oocytes; RN given refers to (S)-isomer; RN for cpd without isomeric designation not avail 5/91 | ||
| willardiine | 3-(uracil-1-yl)-L-alanine : The 3-(uracil-1-yl) derivative of L-alanine. willardiine: isolated from seeds of Acacia willariana; structure | amino acid zwitterion; L-alanine derivative; non-proteinogenic L-alpha-amino acid | |
| (S)-ATPA | (S)-ATPA : A non-proteinogenic L-alpha-amino acid that is L-alanine in which one of the methyl hydrogens is replaced by a 5-tert-butyl-3-hydroxy-isooxazol-4-yl group. | isoxazoles; non-proteinogenic L-alpha-amino acid | metabolite |