Module 9.2: Regulated Secretion - Classical Neurotransmitters vs Neuropeptides

Synthesis and Processing of Peptide Transmitters

• Peptide transmitters are synthesized through translation and processed in the endoplasmic reticulum (ER) and Golgi before being packaged into regulated secretory vesicles at the trans-Golgi network (TGN).
• Dopamine (DOPINE) and neuropeptides mediate slow neurotransmission, while classical transmitters like glutamate receptors can mediate both fast and slow neurotransmission.
• Fast neurotransmission is initiated by ligand-gated ion channels, while slow neurotransmission is initiated by G-protein linked receptors, altering second messengers.
• Synaptic vesicles are not newly formed from the TGN but are transported with other axonal proteins in axonal transport vesicles and are reused multiple times.
• Regulated secretory vesicles, dense core vesicles, and secretory granules are specialized vesicles in endocrine cells and neurons, released only after specific stimuli and cannot be recycled once peptides are released.
• Proteins are sorted into regulated secretory vesicles through aggregation at the TGN, facilitated aggregation, sorting by retention, and association with lipid rafts.
• Chromogranins are acidic proteins that aggregate in the TGN, and their removal affects the formation of dense core vesicles.
• Neuropeptides are always cleaved off a precursor protein, and they have di-basic cleavage sites on either side.
• Neuropeptides have a signal sequence for insertion into the ER through secretory vesicles and may have a glycine signal for amidation.
• Neuropeptides undergo processing including signal sequence cleavage in the ER, endoproteolytic cleavage in the TGN or secretory vesicle, and peptidyl-glycine-alpha-amidation in the vesicle.
• Different processing enzymes cleave neuropeptides in distinct compartments, and the timing of cleavage is important for sorting them.
• The egg-laying hormone is an example that illustrates the importance of timing in the cleavage of neuropeptides.

Test your knowledge of the synthesis and processing of peptide transmitters with this quiz. Explore topics such as the formation of synaptic vesicles, the role of neuropeptides in neurotransmission, and the mechanisms of peptide sorting and cleavage. Perfect for students and professionals in neuroscience, biochemistry, and pharmacology.