Prohormone and proneuropeptide synthesis and secretion

Abstract

Hormones and neuropeptides in eukaryotic cells, are synthesised as large precursor molecules in the rough endoplasmic reticulum (RER), from where they are translocated to the Golgi apparatus. The sorting of proteins destined for the regulated secretory pathway from those which will be released constitutively takes place in the trans-Golgi network (TGN). In both these pathways, vesicles need to be transported to the plasma membrane before their contents can be released by exocytosis. Hormones and neuropeptides need to be secreted from the cells in which are synthesised to exert their biological actions, although they can also play paracrine and autocrine actions. Prohormones and proneuropeptides must undergo post-translational modifications which occur in determined subcellular compartments within eukaryotic cells and are carried out in a strict succession of intracellular events, which give rise to biologically active products. The biosynthesis of prohormones/proneuropeptides is mediated by the action of endoproteolytic enzymes and other post-translational modifying enzymes within the secretory pathway. The major focus of this review will be the biosynthetic pathway, sorting and intracellular trafficking of prohormone and proneuropeptide precursors within the secretory pathway of eukaryotic cells.