2008 Proprotein Processing, Trafficking & Secretion

描述（由申请人提供）： 内分泌和神经内分泌稳态的分子和细胞基础的确定正在发展成为一个令人兴奋但复杂的领域，它提供了对一系列惊人的人类疾病的深入了解。这部分是由于强大的学科的整合，从蛋白质结构和酶学，到蛋白质运输，分泌，以及内分泌稳态中信号肽合成的遗传分析和疾病的病因学，包括糖尿病，癌症和阿尔茨海默氏症以及药物成瘾的生理基础。识别催化数百种肽激素和神经肽成熟的酶是我们理解信号肽和蛋白质生物合成的基础步骤。这些酶的研究提供了一个新的平台，整合前蛋白加工与各种细胞生物学研究，包括蛋白质运输和膜生物合成的调节，特别是高尔基体的动力学和分选，以及刺激耦合内分泌和神经内分泌细胞中致密核心分泌颗粒的形成。激素原转化酶和α-酰胺化酶的分析也为研究另外的膜相关酶系统的作用提供了基础，特别是控制正常细胞中的组织重塑和膜脱落的基质金属蛋白酶和分泌酶，以及它们在促进肿瘤转移和阿尔茨海默病中的破坏。分泌途径蛋白酶系统与导致这些复杂的流行疾病的潜在细胞运输机制一起的合作作用提供了一个强有力的理由，将各种学科聚集在一起，尽可能严格地检查这些因素中的每一个。前蛋白质加工，贩运和分泌戈登研究会议是独一无二的，汇集了来自不同学科的科学家，他们的共同兴趣是信号肽和蛋白质的合成，贩运，加工，分泌和功能。本申请的目的是为年轻的教师，博士后研究员和研究生参加这次会议，唯一一个整合和巩固来自许多生物学科的研究，以阐明前蛋白转化酶，α-酰胺化酶和其他参与内分泌和CNS稳态的加工酶的作用和人类疾病的病因学的财政支持。这次会议将这些研究领域整合到蛋白质运输调节，酵母神经元分泌和胞吐控制以及肽多样性研究的新遗传和生物化学方法的最新进展中。

DESCRIPTION (provided by applicant): 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.