2010 Proprotein Processing, Trafficking, and Secretion; Gordon Research Conferenc

描述(申请人提供)：内分泌和神经内分泌动态平衡的分子和细胞基础的确定已经发展成为一个令人兴奋但复杂的领域，为人们提供了对一系列令人震惊的人类疾病的洞察。这在一定程度上是由于不同学科的整合，从蛋白质结构和酶学，到蛋白质运输，再到内分泌稳态中信号肽合成的遗传分析。这些学科是糖尿病、肥胖症、癌症和阿尔茨海默氏症等疾病病因学的核心，也是药物成瘾的生理基础。对催化数百种多肽激素和神经肽的成熟的酶的鉴定是我们理解信号肽和蛋白质生物合成的基本步骤。这些酶的研究为原蛋白加工与多种细胞生物学研究提供了一个新的平台，包括蛋白质运输和膜生物发生的调节，特别是高尔基体动力学和分选，以及刺激耦合的内分泌和神经内分泌细胞中致密核心分泌颗粒的形成。对PC的分析也为研究额外的膜相关蛋白分解系统，特别是基质金属蛋白酶和分泌酶的作用提供了基础，这些系统控制正常细胞中的组织重塑和膜脱落，以及细胞外各种分子的激活和/或失活，如生长因子和抗菌肽。分泌途径和其他蛋白酶系统在导致糖尿病、癌症、阿尔茨海默病和心脏病等复杂而普遍的疾病的潜在细胞运输机制的背景下所发挥的协同作用，为将这些不同的学科结合在一起以检查疾病状态下分泌途径组成部分的相互作用提供了一个紧迫的理由。前蛋白加工、运输和分泌戈登研究会议的独特之处在于聚集了来自不同学科的科学家，他们对信号肽和蛋白质的合成、运输、加工、分泌和功能有共同的兴趣。这项申请的目的是为这次会议申请资金支持，这是唯一一次整合和巩固来自许多生物学学科的研究，以阐明参与内分泌和中枢神经系统稳态以及在疾病中的处理酶的作用。这次会议整合了这些研究领域的最新进展，包括蛋白质运输的调节，从酵母到神经元的分泌和排泄的控制，以及研究多肽多样性的新的遗传和生化方法。 项目叙事 戈登原蛋白加工、运输和分泌研究会议是一次独特的会议，汇集了来自不同相关学科的科学家，他们对信号肽和蛋白质的合成、运输、加工、分泌和功能有共同的兴趣。此申请的目的是为参加本次会议的年轻教师、博士后研究员和研究生申请资金支持。这是唯一一次整合了多种不同方法来研究原蛋白转换酶、羧基肽酶和其他处理酶在内分泌和中枢神经系统动态平衡和疾病中的作用的会议。

DESCRIPTION (provided by applicant): The determination of the molecular and cellular basis for endocrine and neuroendocrine homeostasis has evolved into an exciting but complex field that provides insight into a staggering array of human diseases. This is in part due to the integration of diverse disciplines ranging from protein structure and enzymology, to protein trafficking, to the genetic analysis of signaling peptide synthesis in endocrine homeostasis. These disciplines are at the heart of the etiology of diseases including diabetes, obesity, cancer and Alzheimer's as well as the physiological basis of drug addiction. The identification of the enzymes--including the proprotein convertases (PCs), select carboxypeptidases, and the a-amidating enzyme --that catalyze the maturation of hundreds of peptide hormones and neuropeptides has been 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 PCs has also provided a foundation to study the role of additional membrane-associated proteolytic systems, particularly the matrix metalloproteases and the secretases, that control tissue remodeling and membrane shedding in normal cells, as well as the extracellular activation and/or inactivation of a variety of molecules such as growth factors and antimicrobial peptides. The cooperative roles of the secretory pathway and other protease systems taken in the context of the underlying cellular trafficking machinery that contributes to complex, prevalent diseases such as diabetes, cancer, Alzheimer's disease, and heart disease, provide an urgent reason to bring together these various disciplines in order to examine the interaction of secretory pathway components in disease states. 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 this conference, the only one to integrate and consolidate research from many biological disciplines in order to illuminate the roles of processing enzymes involved in endocrine and CNS homoeostasis and in 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. Project Narrative The Gordon Research Conference on Proprotein Processing, Trafficking and Secretion is a unique meeting that brings together scientists from a variety of related disciplines whose common interests are 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. This is the only conference that integrates a number of diverse approaches to study the roles of proprotein convertases, carboxypeptidases, and other processing enzymes involved in endocrine and CNS homeostasis and disease.