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

描述（由申请人提供）：确定内分泌和神经内分泌稳态的分子和细胞基础已经发展成为一个令人兴奋但复杂的领域，为人类疾病的惊人阵列提供了洞察力。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的病因学的核心，也是药物成瘾的生理基础。对催化数百种肽激素和神经肽成熟的酶--包括前蛋白转化酶（PC）、选择羧肽酶和α-酰胺化酶--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。PC的分析也提供了一个基础，以研究额外的膜相关的蛋白水解系统的作用，特别是基质金属蛋白酶和分泌酶，控制正常细胞中的组织重塑和膜脱落，以及细胞外激活和/或灭活的各种分子，如生长因子和抗菌肽。分泌途径和其他蛋白酶系统的合作作用的背景下，潜在的细胞运输机制，有助于复杂的，流行的疾病，如糖尿病，癌症，阿尔茨海默氏病，心脏病，提供了一个紧迫的理由，汇集这些不同的学科，以检查疾病状态中的分泌途径组分的相互作用。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。本申请的目的是为本次会议申请财政支持，这是唯一一次整合和巩固来自许多生物学科的研究，以阐明参与内分泌和CNS稳态和疾病的加工酶的作用。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。 项目叙述 戈登前蛋白加工，运输和分泌研究会议是一个独特的会议，汇集了来自各种相关学科的科学家，他们的共同兴趣是合成，运输，加工，分泌和信号肽和蛋白质的功能。此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请求财政支持。这是唯一的会议，整合了许多不同的方法来研究前蛋白转化酶，羧肽酶，和其他加工酶参与内分泌和中枢神经系统稳态和疾病的作用。

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.