neuropeptide processing

Definition

Target type: biologicalprocess

Any protein maturation process achieved by the cleavage of a peptide bond or bonds within a neuropeptide precursor. Processing leads to the attainment of the full functional capacity of the neuropeptide. [PMID:12657671, PMID:17564681]

Neuropeptide processing is a complex and highly regulated process that involves the synthesis, cleavage, and modification of precursor proteins into biologically active peptides. This process ensures the precise generation of functional neuropeptides that play crucial roles in regulating a wide range of physiological functions, including neurotransmission, hormone release, and behavior.

1. **Gene Transcription and Translation:** The process begins with the transcription of neuropeptide precursor genes into messenger RNA (mRNA). mRNA is then translated into a precursor protein, known as a prohormone or proneuropeptide, by ribosomes in the cytoplasm of neurons.

2. **Sorting and Targeting:** Prohormones are sorted and targeted to the appropriate cellular compartments for further processing. They are typically packaged into secretory vesicles, which are small membrane-bound organelles responsible for storing and transporting neuropeptides.

3. **Cleavage by Prohormone Convertases:** Once in secretory vesicles, prohormones undergo enzymatic cleavage by a family of proteases called prohormone convertases (PCs). PCs are highly specific enzymes that recognize and cleave specific amino acid sequences within prohormones. The cleavage process generates individual neuropeptides, often along with other peptides and inactive fragments.

4. **Post-Translational Modifications:** Following cleavage, neuropeptides undergo various post-translational modifications that are essential for their biological activity. These modifications include:
- **Amidation:** The C-terminal amino acid of many neuropeptides is amidated, which increases their stability and potency.
- **Glycosylation:** The addition of sugar molecules can influence neuropeptide solubility, stability, and receptor binding.
- **Phosphorylation:** The addition of phosphate groups can regulate neuropeptide activity and signaling pathways.
- **Acetylation:** The addition of an acetyl group to the N-terminal amino acid can enhance neuropeptide stability and function.

5. **Storage and Release:** Processed neuropeptides are stored within secretory vesicles until they are signaled for release. Upon receiving a neuronal stimulus, the vesicles fuse with the cell membrane and release their cargo into the synaptic cleft or extracellular space.

6. **Neuropeptide Activity:** Released neuropeptides bind to specific receptors on target cells, initiating a cascade of intracellular signaling events that ultimately lead to physiological responses. These responses can range from altering ion channel permeability to modulating gene expression, depending on the neuropeptide and its receptor.

7. **Regulation and Degradation:** The activity of neuropeptides is tightly regulated to ensure proper function. Neuropeptides can be rapidly inactivated by enzymatic degradation or reuptake into the presynaptic neuron. Degradation is often catalyzed by peptidases, which break down neuropeptides into inactive fragments.

Neuropeptide processing is a highly intricate and essential process for the proper functioning of the nervous system and the maintenance of various physiological processes. It is a target for drug development, as manipulating the processing of neuropeptides can potentially alter their activity and provide therapeutic benefits for a range of neurological and endocrine disorders.'
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Proteins (1)

Compounds (18)