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positive regulation of synaptic vesicle recycling

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of synaptic vesicle recycling. [GO_REF:0000058, GOC:pad, GOC:PARL, GOC:TermGenie, PMID:22745285]

Positive regulation of synaptic vesicle recycling is a crucial process for maintaining neurotransmission and neuronal communication. It involves a series of steps that ensure the efficient retrieval and reuse of synaptic vesicles, the small membrane-bound organelles that store and release neurotransmitters. This process is tightly regulated and involves a complex interplay of proteins and signaling pathways.

1. **Endocytosis:** After neurotransmitter release, the vesicle membrane fuses with the presynaptic plasma membrane, leading to the release of neurotransmitters into the synaptic cleft. The fusion process triggers the initiation of endocytosis, the process by which the vesicle membrane is retrieved from the plasma membrane.

2. **Clathrin-mediated endocytosis:** The most common pathway for synaptic vesicle recycling involves the formation of clathrin-coated pits. Clathrin, a protein that forms a cage-like structure, assembles around the region of the plasma membrane where the vesicle membrane is to be retrieved. This assembly is aided by adapter proteins, such as AP-2, which bind to both clathrin and the vesicle membrane.

3. **Dynamin-mediated fission:** Once the clathrin coat is assembled, the vesicle membrane begins to pinch off from the plasma membrane. This process is mediated by the GTPase dynamin, which assembles as a ring around the neck of the budding vesicle. The hydrolysis of GTP by dynamin provides the energy required for vesicle fission.

4. **Uncoating and vesicle reformation:** After fission, the clathrin coat is removed from the newly formed vesicle by the action of Hsc70 and auxilin. The vesicle then undergoes further processing, including the re-uptake of neurotransmitters and the re-acidification of the vesicle lumen.

5. **Vesicle docking and priming:** Once the vesicle is fully reformed, it is transported back to the active zone, the specialized region of the presynaptic terminal where neurotransmitter release occurs. There, the vesicle docks at the active zone and undergoes a priming process, which involves the assembly of the SNARE complex, a protein complex that mediates vesicle fusion with the plasma membrane.

6. **Regulation:** Positive regulation of synaptic vesicle recycling involves a number of factors, including:
* **Calcium signaling:** The influx of calcium ions into the presynaptic terminal following an action potential triggers the exocytosis of synaptic vesicles and initiates the recycling process.
* **Synaptic activity:** The frequency of synaptic activity influences the rate of vesicle recycling.
* **Signaling pathways:** Various signaling pathways, such as the PI3K/Akt and the MAPK pathways, contribute to the regulation of synaptic vesicle recycling.

7. **Importance:** Efficient synaptic vesicle recycling is crucial for maintaining neuronal communication and plasticity. Dysregulation of this process can lead to various neurological disorders, including neurodegenerative diseases and cognitive impairments.

8. **Future directions:** Future research in this area will focus on understanding the precise molecular mechanisms underlying synaptic vesicle recycling, identifying new regulatory proteins, and developing therapeutic approaches to target dysfunctions in this process.'
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Proteins (1)

ProteinDefinitionTaxonomy
Phospholipase A-2-activating proteinA phospholipase A-2-activating protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y263]Homo sapiens (human)

Compounds (10)

CompoundDefinitionClassesRoles
theophyllinedimethylxanthineadenosine receptor antagonist;
anti-asthmatic drug;
anti-inflammatory agent;
bronchodilator agent;
drug metabolite;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
fungal metabolite;
human blood serum metabolite;
immunomodulator;
muscle relaxant;
vasodilator agent
leucineleucine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isobutyl group.

Leucine: An essential branched-chain amino acid important for hemoglobin formation.
amino acid zwitterion;
L-alpha-amino acid;
leucine;
proteinogenic amino acid;
pyruvate family amino acid
algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
phenylalanineL-phenylalanine : The L-enantiomer of phenylalanine.

phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group.

Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
amino acid zwitterion;
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
phenylalanine;
proteinogenic amino acid
algal metabolite;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
Escherichia coli metabolite;
human xenobiotic metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
tryptophantryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3.

Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
L-alpha-amino acid zwitterion;
proteinogenic amino acid;
tryptophan;
tryptophan zwitterion
antidepressant;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
homoarginineL-homoarginine : An L-lysine derivative that is the L-enantiomer of homoarginine.homoarginine;
L-lysine derivative;
non-proteinogenic L-alpha-amino acid
biomarker;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
human metabolite;
rat metabolite;
xenobiotic metabolite
levamisolelevamisole : A 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole that has S configuration. It is used (generally as the monohydrochloride salt) to treat parasitic worm infections in pigs, sheep and cattle and was formerly used in humans as an adjuvant to chemotherapy for the treatment of various cancers. It is also widely used as an adulterant to coccaine.

Levamisole: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)
6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazoleantinematodal drug;
antirheumatic drug;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
immunological adjuvant;
immunomodulator
1-(3,4-dihydroxyphenyl)-2-(1-imidazolyl)ethanonearomatic ketone
1-(3,4-dihydroxyphenyl)-2-[(4,6-dimethyl-2-pyrimidinyl)thio]ethanonearomatic ketone
2,5-dimethoxy-n-(quinolin-3-yl)benzenesulfonamide2,5-dimethoxy-N-(quinolin-3-yl)benzenesulfonamide: a tissue-nonspecific alkaline phosphatase inhibitor; structure in first sourcequinolines
fr 1480835Z-7-oxozeaenol : A macrolide that is the 7-oxo derivative of zeaenol (the 5Z stereoisomer). Isolated from Fungi, it exhibits cytotoxic, antibacterial and inhibitory activity against NF-kappaB.aromatic ether;
macrolide;
phenols;
secondary alcohol;
secondary alpha-hydroxy ketone
antibacterial agent;
antineoplastic agent;
metabolite;
NF-kappaB inhibitor