Proteome and peptidome dynamics

In probably all cells of the body, protein levels are dynamically regulated by a variety of processes. This is especially true of the cells of the neuroendocrine system, which uses proteins and peptides as intercellular messenger molecules. Levels of proteins and peptides are controlled by many steps, including gene transcription, mRNA translation, and posttranslational processing. The formation of neuroendocrine peptides from proteins requires proteolysis at specific sites, and often includes other posttranslational modifications. Some proteolytic steps occur within the cell, prior to secretion, whilst others occur outside the cell following secretion. The extracellular cleavages are not always degradative; some cleavages increase the bioactivity of certain peptides while others inactivate the peptides. Similarly, the intracellular proteolytic steps are not always activating; some of the cleavages change the specificity of a peptide and alter its bioactivity. Thus, the production of bioactive proteins and peptides is a highly dynamic process that is regulated in multiple ways. Most of the research on bioactive endocrine peptides has focused on those produced within the secretory pathway, and these are the major focus of this review. In addition to these peptides, the concepts of non-classic neuropeptides and bioactive intracellular peptides are also discussed. The emerging idea is that peptides are capable of affecting many diverse cellular processes, including protein-protein interactions. The finding that the brain contains a large number of peptides derived from cytosolic, nuclear, and mitochondrial proteins raises the intriguing possibility that these peptides are also functional. These novel concepts are discussed, with a focus on the dynamics of the proteome and peptidome.