synaptic vesicle targeting
Definition
Target type: biologicalprocess
The process in which synaptic vesicles are directed to specific destination membranes, mediated by molecules at the vesicle membrane and target membrane surfaces. [GOC:mah]
Synaptic vesicle targeting is a complex and highly regulated process that ensures the precise delivery of neurotransmitters to the synaptic cleft. It involves a series of intricate steps that orchestrate the movement of synaptic vesicles from their site of synthesis in the cell body to the presynaptic terminal, where they dock and fuse with the plasma membrane, releasing their contents.
The journey begins with the formation of synaptic vesicles in the Golgi apparatus, where they bud off as small, membrane-bound spheres filled with neurotransmitters. These nascent vesicles are then transported along microtubules, the cellular highways of the neuron, towards the presynaptic terminal. This transport is mediated by motor proteins like kinesin and dynein, which use ATP hydrolysis to move the vesicles along the microtubule tracks.
Upon reaching the presynaptic terminal, synaptic vesicles undergo a series of docking and priming events. These events involve the interaction of specific proteins on the vesicle membrane with proteins on the presynaptic membrane. The key players in this process include the SNARE proteins: synaptobrevin (V-SNARE), syntaxin (T-SNARE), and SNAP-25 (T-SNARE). These proteins form a complex that bridges the vesicle and plasma membranes, bringing them into close proximity.
Once docked, synaptic vesicles are primed for fusion. This involves the assembly of a fusion machinery that includes proteins like synaptotagmin and complexin. Synaptotagmin acts as a calcium sensor, triggering vesicle fusion upon the influx of calcium ions into the presynaptic terminal.
The final step in synaptic vesicle targeting is fusion. When calcium binds to synaptotagmin, it induces a conformational change that promotes the assembly of a fusion pore between the vesicle and plasma membranes. This pore expands, allowing the neurotransmitter to be released into the synaptic cleft, where it can bind to receptors on the postsynaptic neuron.
After fusion, synaptic vesicles are rapidly recycled through endocytosis. This process retrieves the vesicle membrane and neurotransmitter from the synaptic cleft, replenishing the pool of vesicles available for future release. Endocytosis is also a highly regulated process, involving proteins like clathrin and dynamin.
In summary, synaptic vesicle targeting is a multi-step process that involves vesicle formation, transport, docking, priming, fusion, and recycling. It is a critical event in neuronal communication, ensuring the precise and efficient delivery of neurotransmitters to the synaptic cleft.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Presenilin-1 | A presenilin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49768] | Homo sapiens (human) |
Compounds (22)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tocopheroxy radical | tocopheroxy radical: RN given refers to radical ion (1+), (2R-(2R*(4R*,8R*)))-isomer; RN for cpd without isomeric designation not available 12/90 | tocopherol | |
| 7-amino-4-chloro-3-methoxy-2-benzopyran-1-one | isocoumarins | ||
| tarenflurbil | tarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein; | flurbiprofen | |
| cholanic acid | 5beta-cholanic acids; cholanic acid | ||
| t0901317 | T0901317: an LXRalpha and LXRbeta agonist | ||
| n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester | DAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor. | carboxylic ester; difluorobenzene; dipeptide; tert-butyl ester | EC 3.4.23.46 (memapsin 2) inhibitor |
| sulindac sulfide | sulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity. sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source | aryl sulfide; monocarboxylic acid; organofluorine compound | antineoplastic agent; apoptosis inducer; non-steroidal anti-inflammatory drug |
| l 685458 | L 685458: a gamma-secretase inhibitor; structure in first source L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease. | carbamate ester; monocarboxylic acid amide; peptide; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor; peptidomimetic |
| mk 0752 | |||
| ly 450139 | peptide | ||
| chf 5074 | 1-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source | ||
| ly 411575 | dibenzoazepine; difluorobenzene; lactam; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor | |
| 4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acid | sulfonamide | ||
| begacestat | |||
| e 2012 | |||
| mrk 560 | MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source | ||
| 1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone | 1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source | ||
| pf 3084014 | nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment. nirogacestat: an antineoplastic agent | ||
| bms 708163 | BMS 708163: structure in first source | oxadiazole; ring assembly | |
| ro 4929097 | dibenzoazepine; dicarboxylic acid diamide; lactam; organofluorine compound | EC 3.4.23.46 (memapsin 2) inhibitor | |
| jnj 40418677 | |||
| (r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline | (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source |