Page last updated: 2024-10-24

anterograde neuronal dense core vesicle transport

Definition

Target type: biologicalprocess

The directed movement of substances in neuronal dense core vesicles along axonal microtubules towards the presynapse. [GOC:kmv, PMID:23358451]

Anterograde neuronal dense core vesicle (DCV) transport is a fundamental process for communication between neurons. It involves the movement of DCVs from the cell body, or soma, to the axon terminal, where they release their cargo, typically neuropeptides and other signaling molecules, into the synaptic cleft. Here's a detailed breakdown of the process:

**1. Biosynthesis and Sorting:**
- Neuropeptides and other DCV cargo are synthesized in the soma and undergo modifications in the endoplasmic reticulum (ER) and Golgi apparatus.
- Specialized sorting machinery, including adaptor proteins and sorting receptors, direct cargo molecules to the trans-Golgi network (TGN).
- At the TGN, cargo molecules are packaged into nascent DCVs, which bud off from the Golgi membrane.

**2. Immature DCV Maturation:**
- Immature DCVs are characterized by their relatively small size and lack of mature protein content.
- They undergo a series of maturation steps as they travel along the axon, including:
- Acquisition of additional cargo proteins, such as neuropeptides and enzymes.
- Accumulation of specific lipids, which alter the vesicle membrane composition.
- Modification of the vesicle coat proteins.

**3. Axonal Transport:**
- Mature DCVs are transported along the axon towards the synapse, propelled by motor proteins that bind to the vesicle membrane.
- The primary motor protein involved in anterograde DCV transport is kinesin, which uses ATP hydrolysis to move along microtubule tracks.
- The microtubule network in the axon provides a structural scaffold for efficient transport.

**4. Synaptic Docking and Fusion:**
- Upon reaching the axon terminal, DCVs undergo a series of events that lead to their docking and fusion with the presynaptic membrane.
- Docking involves interactions between specific proteins on the vesicle and the presynaptic plasma membrane, anchoring the vesicle in place.
- Fusion requires the coordinated action of multiple proteins, including SNARE proteins, which mediate membrane fusion and release of the DCV contents into the synaptic cleft.

**5. Cargo Release and Signal Transduction:**
- Upon fusion, the neuropeptides and other signaling molecules contained within the DCV are released into the synaptic cleft.
- These molecules bind to specific receptors on the postsynaptic neuron, triggering a cascade of signaling events that ultimately lead to changes in neuronal activity.

**6. Vesicle Recycling:**
- After release, DCVs undergo a recycling process to replenish the pool of vesicles available for future release.
- This involves endocytosis of the vesicle membrane, followed by sorting and re-packaging of cargo molecules.

Anterograde neuronal DCV transport is a tightly regulated process involving a complex interplay of proteins, lipids, and signaling pathways. It is essential for neuronal communication and plays a crucial role in diverse brain functions, including learning, memory, and behavior.'
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Proteins (1)

ProteinDefinitionTaxonomy
Kinesin-1 heavy chainA kinesin-1 heavy chain that is encoded in the genome of human. [PRO:DNx, UniProtKB:P33176]Homo sapiens (human)

Compounds (5)

CompoundDefinitionClassesRoles
whi p180
staurosporineindolocarbazole alkaloid;
organic heterooctacyclic compound
apoptosis inducer;
bacterial metabolite;
EC 2.7.11.13 (protein kinase C) inhibitor;
geroprotector
zd 6474CH 331: structure in first sourcearomatic ether;
organobromine compound;
organofluorine compound;
piperidines;
quinazolines;
secondary amine
antineoplastic agent;
tyrosine kinase inhibitor
lenvatiniblenvatinib : A member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine.aromatic amide;
aromatic ether;
cyclopropanes;
monocarboxylic acid amide;
monochlorobenzenes;
phenylureas;
quinolines
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist;
orphan drug;
vascular endothelial growth factor receptor antagonist
cabozantinibcabozantinib : A dicarboxylic acid diamide that is N-phenyl-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in which the hydrogen at position 4 on the phenyl ring is substituted by a (6,7-dimethoxyquinolin-4-yl)oxy group. A multi-tyrosine kinase inhibitor, used (as its malate salt) for the treatment of progressive, metastatic, medullary thyroid cancer.

cabozantinib: a multikinase inhibitor
aromatic ether;
dicarboxylic acid diamide;
organofluorine compound;
quinolines
antineoplastic agent;
tyrosine kinase inhibitor