Target type: biologicalprocess
The biological process in which a synapse between a motor neuron and a muscle is initially formed. [GOC:isa_complete]
The establishment of synaptic specificity at the neuromuscular junction (NMJ) is a complex and fascinating process that ensures precise communication between motor neurons and muscle fibers. This specificity is crucial for coordinated muscle movement and is achieved through a series of molecular interactions and signaling events. Here's a detailed description of this process:
**1. Axon Guidance and Target Recognition:**
- Motor neuron axons navigate through the developing embryo to reach their target muscle fibers. This journey involves several guidance cues, including chemoattractants and chemorepellents, which direct the axons along specific pathways.
- Once the axons reach the vicinity of the muscle, they recognize specific molecules on the muscle fiber surface, known as "target recognition molecules." These molecules trigger signaling cascades within the axon, promoting its growth and differentiation.
**2. Synaptic Aggregation and Differentiation:**
- Once an axon finds its target muscle fiber, it forms a specialized structure called a synapse. This involves the aggregation of presynaptic and postsynaptic components at the contact point.
- At the presynaptic terminal, the axon releases acetylcholine (ACh), a neurotransmitter that transmits signals across the synapse. This involves the accumulation of synaptic vesicles filled with ACh and the clustering of proteins involved in ACh release.
- At the postsynaptic side, the muscle fiber develops specialized receptors called acetylcholine receptors (AChRs) that bind to ACh. This clustering of AChRs is essential for efficient signal transduction.
**3. Synapse Maturation and Refinement:**
- The newly formed synapse undergoes further maturation and refinement, stabilizing its structure and function.
- This involves the precise alignment of presynaptic and postsynaptic components, ensuring that ACh is released directly onto the AChRs.
- The synapse also undergoes activity-dependent plasticity, meaning that its structure and function can be modified by the patterns of neuronal activity. This allows the synapse to adapt to changing demands and refine its communication.
**4. Role of Molecular Players:**
- Several key molecules play critical roles in establishing synaptic specificity at the NMJ.
- **Agrin** is a protein secreted by motor neurons that triggers the clustering of AChRs at the postsynaptic membrane.
- **Muscle-specific kinase (MuSK)** is a receptor tyrosine kinase on muscle fibers that binds to agrin and initiates downstream signaling pathways leading to AChR clustering.
- **Neuregulin** is another signaling molecule that contributes to synapse formation and maintenance.
- **Synaptic adhesion molecules** like **neuroligins** and **neurexins** promote the adhesion of presynaptic and postsynaptic terminals.
**5. Significance of Synaptic Specificity:**
- The precise establishment of synaptic specificity at the NMJ is essential for coordinated muscle movement.
- It ensures that each motor neuron innervates the correct muscle fiber, allowing for precise control of muscle contractions.
- Any disruption in this process can lead to muscle weakness, paralysis, or other neurological disorders.
**6. Developmental and Plasticity:**
- Synaptic specificity is established during development but can be modified throughout life. This plasticity allows the nervous system to adapt to changing needs and experiences.
- For example, during learning and memory formation, synapses can be strengthened or weakened, reflecting the changing patterns of neuronal activity.
- This plasticity is essential for maintaining and refining motor skills and adapting to new challenges.
**In summary, the establishment of synaptic specificity at the neuromuscular junction involves a complex interplay of molecular signaling, cell adhesion, and activity-dependent plasticity. This process ensures precise communication between motor neurons and muscle fibers, allowing for coordinated muscle movement and adaptation to changing demands.**'"
Protein | Definition | Taxonomy |
---|---|---|
Proteinase-activated receptor 1 | A proteinase-activated receptor 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P25116] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one | 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source | chromones; morpholines; organochlorine compound | autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector |
ultram | 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol : A tertiary alcohol that is cyclohexanol substituted at positions 1 and 2 by 3-methoxyphenyl and dimethylaminomethyl groups respectively. | aromatic ether; tertiary alcohol; tertiary amino compound | |
omega-n-methylarginine | N(omega)-methyl-L-arginine : A L-arginine derivative with a N(omega)-methyl substituent. omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase. | amino acid zwitterion; arginine derivative; guanidines; L-arginine derivative; non-proteinogenic L-alpha-amino acid | |
vu0099704 | VU0099704: an antagonist of protease activated receptor 4 (PAR-4); structure in first source | ||
2-bromo-N-[3-(1-oxopropylamino)phenyl]benzamide | benzamides | ||
2-bromo-N-[3-(1-oxobutylamino)phenyl]benzamide | benzamides | ||
sch 79797 | quinazolines | ||
morphine | Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn. | morphinane alkaloid; organic heteropentacyclic compound; tertiary amino compound | anaesthetic; drug allergen; environmental contaminant; geroprotector; mu-opioid receptor agonist; opioid analgesic; plant metabolite; vasodilator agent; xenobiotic |
tapentadol | Tapentadol: An opioid analgesic, MU OPIOID RECEPTOR agonist, and noradrenaline reuptake inhibitor that is used in the treatment of moderate to severe pain, and of pain associated with DIABETIC NEUROPATHIES. | alkylbenzene | |
o-demethyltramadol | alkylbenzene; ring assembly | ||
rwj-56110 | RWJ-56110: a PAR-1 antagonist; structure in first source | ||
vorapaxar | vorapaxar : A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation. vorapaxar: has antiplatelet activity; structure in first source | carbamate ester; lactone; naphthofuran; organofluorine compound; pyridines | cardiovascular drug; platelet aggregation inhibitor; protease-activated receptor-1 antagonist |
e 5555 | E 5555: a 2-iminopyridine derivative and platelet aggregation inhibitor | aromatic ketone | |
zstk474 | ZSTK-474 : A triamino-1,3,5-triazine that is 1,3,5-triazine in which two of the hydrogens have been replaced by morpholin-4-yl groups while the third hydrogen has been replaced by a 2-(difluoromethyl)benzimidazol-1-yl group. It is an inhibitor of phosphatidylinositol 3-kinase. | benzimidazoles; morpholines; organofluorine compound; triamino-1,3,5-triazine | antineoplastic agent; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor |
AZ3451 | benzimidazoles; benzodioxoles; nitrile; organobromine compound; secondary carboxamide | anti-inflammatory agent; autophagy inducer; PAR2 negative allosteric modulator |