Trafficking of the vasopressin and oxytocin prohormone through the regulated secretory pathway

The trafficking of prohormones and of regulated secretory proteins in gener al has been studied extensively in the last decades of the last century. Pr ohormone trafficking starts with correct folding and subsequently efficient sorting into the secretory granule of the regulated secretory pathway. The vasopressin/oxytocin prohormone is particularly interesting for studying p rotein trafficking, because the physicochemical properties and three-dimens ional structure have been largely elucidated. In the case of pro-vasopressi n and pro-oxytocin, folding and sorting depend completely on both intramole cular and intermolecular interactions. Proper folding is guided by the horm one-neurophysin association and the sorting event relies on the aggregative properties of the neurophysin domain in the prohormone, as well as a speci fic sorting signal, which is revealed when the aggregative property of the neurophysin domain is deleted. A comprehensive mechanism for trafficking of the vasopressin/oxytocin prohormone from the endoplasmic reticulum to the secretory granule is proposed.