2008 Proprotein Processing, Trafficking & Secretion

2008 年前蛋白加工、贩运

基本信息

批准号：
7536669
负责人：
RICHARD E MAINS
金额：
$ 1.5万
依托单位：
GORDON RESEARCH CONFERENCES
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7536669
关键词：
Alzheimer&apos s Disease Anabolism Area Biochemical Genetics Biological Cells Complex Diabetes Mellitus Discipline Disease Drug Addiction Endocrine Endopeptidases Enzymatic Biochemistry Enzymes Etiology Exocytosis Faculty Financial Support Foundations Golgi Apparatus Homeostasis Malignant Neoplasms Membrane Metalloproteases Molecular Neoplasm Metastasis Neuroendocrine Cell Neurons Neuropeptides Neurosecretory Systems Normal Cell Pathway interactions Peptide Hydrolases Peptide Signal Sequences Peptide Synthesis Peptides Physiological Postdoctoral Fellow Process Prohormone Convertase Proprotein Convertases Proteins Purpose Range Regulation Research Role Scientist Secretory Vesicles Sorting - Cell Movement Stimulus Students System Tissues Yeasts base genetic analysis human disease insight interest intracellular protein transport membrane biogenesis novel peptide hormone protein structure protein transport secretase secretion process symposium trafficking tumor

项目摘要

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.

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演变成一个令人兴奋但复杂的领域，它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强大学科的整合，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，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。催化数百种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本一步。这些酶的研究提供了一个新的平台，将前蛋白加工与各种细胞生物学研究相结合，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，以及刺激中致密核心分泌颗粒的形成。内分泌细胞和神经内分泌细胞耦合。对激素原转化酶和α-酰胺化酶的分析也为研究其他膜相关酶系统的作用提供了基础，特别是基质金属蛋白酶和控制正常细胞中组织重塑和膜脱落的分泌酶，以及它们的作用。颠覆促进肿瘤转移和阿尔茨海默病。分泌途径蛋白酶系统与导致这些复杂、流行疾病的潜在细胞运输机制的协同作用提供了强有力的理由，将各种学科聚集在一起，尽可能严格地检查每个因素。前蛋白加工、运输和分泌戈登研究会议的独特之处在于，来自不同学科的科学家聚集在一起，他们的共同兴趣是信号肽和蛋白质的合成、运输、加工、分泌和功能。本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请求经济支持，这是唯一一个整合和巩固来自许多生物学科的研究的会议，以阐明前蛋白转化酶（a-酰胺化酶和其他参与内分泌和中枢神经系统稳态以及人类疾病病因学的加工酶。本次会议将这些研究领域整合到蛋白质运输调节、从酵母到神经元的分泌和胞吐作用的控制以及肽多样性研究的新遗传和生化方法方面的最新进展。