? ? The determination of the molecular and cellular bases of endocrine and neuroendocrine homeostasis is evolving into an exciting but complex field, one that provides insight into a staggering array of human diseases. This is in part due to the integration of powerful disciplines ranging from protein structure and enzymology, to protein trafficking, secretion, and the genetic analysis of signaling peptide synthesis in endocrine homeostasis and the etiology of diseases including diabetes, cancer and Alzheimer's as well as the physiological basis of drug addiction. The identification of the enzymes that catalyze the maturation of hundreds of peptide hormones and neuropeptides was a fundamental step in our understanding of the biosynthesis of signaling peptides and proteins. The study of these enzymes has provided a novel platform to integrate proprotein processing with a variety of cell biological studies, including the regulation of protein traffic and membrane biogenesis, especially Golgi dynamics and sorting, and the formation of dense-core secretory granules in stimulus-coupled endocrine and neuroendocrine cells. Analysis of the Prohormone Convertases and the a-Amidating Enzyme has also provided a foundation to study the role of additional membrane-associated enzymatic systems, particularly the matrix metalloproteases and the secretases that control tissue remodeling and membrane shedding in normal cells, as well as their subversion in promoting tumor metastasis and Alzheimer's disease. The cooperative roles of the secretory pathway protease systems together with the underlying cellular trafficking machinery that contribute to these complex, prevalent diseases provides a potent reason to bring together various disciplines to examine each of these factors as rigorously as possible. The Proprotein Processing, Trafficking and Secretion Gordon Research Conference is unique in bringing together scientists from a variety of disciplines whose common interest is in the synthesis, trafficking, processing, secretion, and function of signaling peptides and proteins. The purpose of this application is to request financial support for young faculty, postdoctoral fellows and graduate students to attend this conference, the only one to integrate and consolidate research from many biological disciplines in order to illuminate the roles of the proprotein convertases, the a- amidating enzyme and other processing enzymes involved in endocrine and CNS homoeostasis and the etiology of human disease. This conference integrates these areas of study into recent advances in the regulation of protein traffic, the control of secretion and exocytosis from yeast to neurons, and novel genetic and biochemical approaches to the study of peptide diversity. ? ? ?
| Couture, Frederic; D'Anjou, Francois; Day, Robert (2011) On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications. Biomol Concepts 2:421-438 |
