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CONTROL OF MEMBRANE TRAFFIC IN REGULATED SECRETORY CELLS

调节分泌细胞中膜流量的控制

基本信息

批准号：
2177809
负责人：
HSIAO-PING H MOORE
金额：
$ 17.99万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-07-01 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2177809
关键词：
Golgi apparatus guanine nucleotide binding protein hormone regulation /control mechanism intracellular membranes intracellular transport laboratory mouse laboratory rabbit laboratory rat membrane activity molecular cloning nucleic acid sequence peptide hormone polymerase chain reaction protein transport secretion site directed mutagenesis vesicle /vacuole

项目摘要

The long term goal of this proposal is to understand the molecular machinery involved in intracellular membrane transport and secretion in neural, endocrine, and exocrine cells. Most cells have the capacity to secrete proteins, but not all cells utilize the same machinery. In particular, secretion from mammalian cells can take many different forms. The different pathways enable the cells to externalize molecules in a timely and spatially regulated fashion. These pathways together control a variety of cellular processes, including plasma membrane growth, cell-cell communication, and regulation of cell surface transport activities. Currently, little is known about the molecular components controlling export from each pathway, and how the machinery differ from one another. Neuroendocrine cells will be used as a model system to study two secretory pathways: a constitutive pathway and a regulated pathway. Exocytotic vesicles involved in these two secretory pathways are formed from the same organelle, the trans-Golgi network. Thus, our studies will be aimed at understanding the mechanisms for transport between the trans-Golgi network and the cell surface along both paths. The specific goals of these studies are: (1) to elucidate the mechanism for the formation of constitutive and regulated vesicles from the trans-Golgi network; proteins that may participate in these processes will be identified and their roles in vesicle budding will be tested in an in vitro assay that reconstitutes transport; (2) to study the components involved in vesicle targeting and fusion. GTP binding proteins and their accessory proteins involved in these processes will be identified and studied. Whether these factors are unique to the individual pathway will be determined; (3) to study the mechanism for sorting of proteins between the constitutive and the regulated pathways. Structural determinants important for sorting will be defined by mutagenesis studies. The current model for sorting will be examined by an in vivo test to determine if sorting of hormones into the regulated secretory pathway is achieved by formation of molecular aggregates.

该提案的长期目标是了解分子参与细胞内膜运输和分泌的机制神经细胞、内分泌细胞和外分泌细胞。大多数细胞都有能力分泌蛋白质，但并非所有细胞都利用相同的机制。在特别是，哺乳动物细胞的分泌可以采取许多不同的形式。不同的途径使细胞能够将分子外化时间和空间调节的时尚。这些途径共同控制各种细胞过程，包括质膜生长、细胞间生长通信和细胞表面运输活动的调节。目前，人们对控制的分子成分知之甚少。每个路径的输出，以及机器之间的差异。神经内分泌细胞将用作模型系统来研究两种分泌细胞途径：组成型途径和调节途径。胞吐参与这两种分泌途径的囊泡是由相同的细胞器，跨高尔基体网络。因此，我们的研究将旨在了解跨高尔基体网络之间的运输机制以及沿两条路径的细胞表面。这些研究的具体目标主要有：（1）阐明本构性和结构性的形成机制。来自跨高尔基体网络的调节囊泡；蛋白质可能参与这些过程的人员将被确定，并且他们在其中的角色囊泡出芽将在体外测定中进行测试，该测定可重构运输; (2) 研究参与囊泡靶向的成分融合。 GTP 结合蛋白及其辅助蛋白参与这些过程将得到确定和研究。这些因素是否将确定个人途径所特有的； (3) 研究蛋白质在组成型和结构型之间的分类机制受监管的途径。对于排序来说重要的结构决定因素是由诱变研究定义。当前的排序模型将是通过体内测试进行检查以确定激素是否分类调节的分泌途径是通过形成分子来实现的聚合体。