2008 Proprotein Processing, Trafficking & Secretion

描述(由申请人提供)： 内分泌和神经内分泌动态平衡的分子和细胞基础的测定正在演变成一个令人兴奋但复杂的领域，这个领域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从蛋白质结构和酶学到蛋白质运输、分泌和内分泌稳态信号肽合成的遗传分析等强大学科的整合，以及糖尿病、癌症和阿尔茨海默氏症等疾病的病因学以及药物成瘾的生理基础。对催化数百种多肽激素和神经肽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础步骤。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。对前激素转换酶和α-胺化酶的分析也为研究额外的膜相关酶系统，特别是控制正常细胞中组织重塑和膜脱落的基质金属蛋白酶和分泌酶的作用，以及它们在促进肿瘤转移和阿尔茨海默病中的颠覆提供了基础。分泌途径蛋白水解酶系统的协同作用以及导致这些复杂、流行疾病的潜在细胞运输机制提供了一个强有力的理由，需要将不同的学科聚集在一起，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。这项申请的目的是请求财政支持，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的研究，从许多生物学学科，以阐明原蛋白转换酶，α-氨基酶和其他处理酶涉及内分泌和中枢神经系统稳态和人类疾病的病因学的作用。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。

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.