Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of calcium ion-dependent exocytosis of neurotransmitter. [GO_REF:0000058, GOC:TermGenie, PMID:16782817]
Calcium ion-dependent exocytosis of neurotransmitter is a fundamental process in neuronal communication. It involves the release of neurotransmitters from synaptic vesicles into the synaptic cleft, triggered by an influx of calcium ions. The process can be broken down into several key steps:
1. **Action Potential Arrival**: The arrival of an action potential at the presynaptic terminal depolarizes the membrane, opening voltage-gated calcium channels.
2. **Calcium Influx**: Calcium ions flow into the presynaptic terminal down their electrochemical gradient. The concentration of calcium within the terminal increases dramatically.
3. **Vesicle Docking and Priming**: Synaptic vesicles containing neurotransmitters are tethered to the presynaptic membrane and primed for fusion. This process involves a complex interplay of proteins like SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors), synaptotagmin, and complexins.
4. **Calcium Sensing and Fusion**: Calcium ions bind to synaptotagmin, a calcium sensor protein. This binding event triggers a conformational change in synaptotagmin, which interacts with SNAREs, promoting the fusion of the vesicle membrane with the presynaptic membrane.
5. **Exocytosis**: The fusion of the vesicle membrane with the plasma membrane results in the release of neurotransmitter into the synaptic cleft.
6. **Endocytosis**: After neurotransmitter release, the vesicle membrane is retrieved through endocytosis, forming a new vesicle. This process is essential for replenishing the pool of synaptic vesicles.
The regulation of this process is intricate and involves various factors.
**Regulation of Calcium Entry**:
- **Voltage-gated calcium channels**: The opening and closing of these channels are regulated by membrane potential, influencing the amount of calcium entering the presynaptic terminal.
- **Calcium channel modulators**: Various proteins and molecules can bind to and modulate calcium channel activity, affecting calcium influx.
**Regulation of Vesicle Docking and Priming**:
- **SNARE complex formation**: The assembly and disassembly of the SNARE complex are crucial for vesicle docking and priming, and can be influenced by signaling pathways.
- **Synaptotagmin**: The calcium binding properties of synaptotagmin are critical for regulating the timing and efficiency of exocytosis.
**Regulation of Fusion**:
- **Calcium concentration**: The concentration of calcium ions in the presynaptic terminal directly influences the rate of exocytosis.
- **Other signaling pathways**: Various signaling pathways can modulate the activity of proteins involved in exocytosis, impacting the release of neurotransmitter.
The precise mechanism of calcium-dependent exocytosis can vary depending on the type of neurotransmitter, the specific synapse, and the neuronal cell type. Understanding the intricate interplay of these factors is crucial for comprehending neuronal communication and the pathogenesis of neurological disorders.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 | A sarcoplasmic/endoplasmic reticulum calcium ATPase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P16615] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 2,5-di-tert-butylhydroquinone | 2,5-di-tert-butylbenzene-1,4-diol : A member of the class of hydroquinones that is benzene-1,4-diol substituted by tert-butyl groups at position 2 and 5. | hydroquinones | |
| paxilline | paxilline : An indole diterpene alkaloid with formula C27H33NO4 isolated from Penicillium paxilli. It is a potent inhibitor of large conductance Ca2(+)- and voltage-activated K(+) (BK)-type channels. paxilline: structure given in first source; RN given refers to (2R-(2alpha,4bbeta,6aalpha,12bbeta,12calpha,14abeta))-isomer | diterpene alkaloid; enone; organic heterohexacyclic compound; terpenoid indole alkaloid; tertiary alcohol | anticonvulsant; Aspergillus metabolite; EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor; genotoxin; geroprotector; mycotoxin; Penicillium metabolite; potassium channel blocker |
| curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
| biselyngbyaside | biselyngbyaside: antineoplastic from the marine cyanobacterium Lyngbya sp.; structure in first source | ||
| alpha-cyclopiazonic acid | alpha-cyclopiazonic acids |