negative regulation of excitatory synapse assembly

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of excitatory synapse assembly. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie]

Negative regulation of excitatory synapse assembly is a crucial process that fine-tunes the strength and specificity of neuronal communication. It involves a complex interplay of molecular mechanisms that act to suppress or dampen the formation of excitatory synapses, ensuring proper circuit development and preventing excessive excitation.

Here's a detailed breakdown of the key aspects involved:

**1. Transcriptional Regulation:**
* **Repression of Synaptic Gene Expression:** Transcription factors, such as REST (RE1-silencing transcription factor), are known to repress the expression of genes involved in excitatory synapse formation, including those encoding synaptic adhesion molecules, neurotransmitter receptors, and scaffolding proteins.
* **MicroRNA-mediated Regulation:** MicroRNAs, small non-coding RNAs, can target specific mRNAs involved in excitatory synapse development for degradation or translational repression. For instance, miR-134 has been shown to suppress the translation of the GluA1 subunit of the AMPA receptor, a key component of excitatory synapses.

**2. Post-translational Modifications:**
* **Protein Phosphorylation and Deacetylation:** Kinases and phosphatases regulate the activity of proteins involved in synapse formation. For example, phosphorylation of the NR2B subunit of the NMDA receptor can enhance its activity, while deacetylation of the PSD-95 scaffold protein can reduce synapse strength.
* **Ubiquitylation and Degradation:** The ubiquitin-proteasome system plays a role in targeting proteins for degradation. This process can remove proteins that promote excitatory synapse formation, thereby reducing synapse strength.

**3. Trans-Synaptic Signaling:**
* **Neuregulin 1 (NRG1):** This transmembrane protein acts as a retrograde signal from the postsynaptic neuron to the presynaptic neuron, inhibiting the release of neurotransmitters.
* **Ephrins:** This family of transmembrane ligands can trigger signaling cascades in both presynaptic and postsynaptic neurons, contributing to the negative regulation of synapse assembly.

**4. Synaptic Pruning:**
* **Microglia:** These immune cells are crucial for eliminating synapses that are not properly formed or are no longer needed. They phagocytose synaptic components, effectively pruning weak or redundant synapses.
* **Complement System:** The complement system, a part of the immune system, can be activated in the context of synapse pruning. This can lead to the tagging of synapses for elimination by microglia.

**5. Developmental Regulation:**
* **Activity-dependent Regulation:** Neuronal activity plays a significant role in regulating synapse assembly. Synapses that are not frequently used are more likely to be pruned, while those that are active are strengthened.
* **Developmental Stage:** The balance between excitatory and inhibitory synaptic activity changes throughout development. During early stages, there is a greater emphasis on excitatory synapse formation, but as the nervous system matures, the negative regulation of excitatory synapse assembly becomes increasingly important.

**Conclusion:** Negative regulation of excitatory synapse assembly is a highly regulated process that ensures proper circuit development and prevents excessive excitation. This intricate interplay of molecular mechanisms, including transcriptional and post-translational regulation, trans-synaptic signaling, and synaptic pruning, fine-tunes neuronal communication, contributing to the sophisticated function of the nervous system.'
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Proteins (1)

Compounds (1)