CONTROL OF VESICULAR CARRIER TRAFFIC IN HEPATOCYTES
肝细胞中囊泡载体运输的控制
基本信息
- 批准号:6237384
- 负责人:
- 金额:$ 16.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-06-20 至 1998-05-31
- 项目状态:已结题
- 来源:
- 关键词:G protein Golgi apparatus antibody receptor antiidiotype antibody basolateral membrane blocking antibody cell membrane endocytosis eukaryote exocytosis immunoaffinity chromatography intracellular transport laboratory mouse laboratory rabbit laboratory rat liver cells membrane activity membrane fusion membrane proteins transcytosis vesicle /vacuole
项目摘要
This project is focused on the isolation and characterization of
vesicular carriers known to operate in eukaryotic cells at each relay
along the endoplasmic reticulum-plasmalemma pathway, its branches, and,
in addition, across epithelial and glandular cells. The vesicular
carriers are an integral and important part of the system that controls
intracellular protein and membrane traffic. The system distributes
efficiently and accurately proteins produced in a single cell compartment
(the cytosol) to more than twenty sites (membranes and compartments) of
final functional residence. Traffic to the ER is controlled protein by
protein, but from the ER-Golgi junction downstream, proteins are sorted
individually and transported in sorted batches by specific vesicular
carriers to their different destinations to which the carriers are
directed by specific pilots. The basic premise of the project is that
sorters and pilots, i.e., the key elements of the traffic control system,
are integral membrane proteins of the vesicular carriers and that the
first step towards their identification is the isolation and
characterization of specific classes of vesicular carriers. We propose
the use the liver of the intact rat, or perfused rat livers or primary
cultures of rat hepatocytes, as convenient sources of vesicular carriers
and we have a reliable marker, the polymeric IgA receptor, whose form and
time of peak labeling are characteristic for each major class of
vesicular carriers. We have recently isolated, by immunoadsorption, a
fraction of transcytotic vesicular carriers. We propose to complete its
characterization and reconstitute the last step in transcytosis in a
cell-free system using as donor the fraction mentioned above and, as
acceptor, a plasmalemmal fraction that includes the proper target. We
propose to raise antibodies to the integral membrane proteins of the
carrier and test them for their ability to block fusion with the target.
The cognate antigen will be further investigated as a putative pilot.
Anti-idiotypic antibodies will be tested as a potential tool for
isolating sorters. We intend to take advantage of the cholestatic liver
as a source of transcytotic carriers defective in terminal vesicular
fusion. We intend to proceed towards the isolation and characterization
of vesicular carriers operating at the trans Golgi-sinusoidal domain of
the plasmalemma relay to find out if different or the same carriers are
involved in the transport of secretory and membrane proteins. Since this
work concentrates on the vesicular carriers themselves, it will
complement current work on cytosolic factors required for vesicular
transport. Interaction between the two approaches is expected to advance
our understanding of the overall traffic control system.
本项目的重点是分离和鉴定
已知的囊泡载体在真核细胞中的每一次传递
沿着内质网-质膜途径,它的分支,和,
此外,横跨上皮细胞和腺体细胞。水泡
载体是控制系统中不可或缺的重要部分
胞内蛋白质和膜交通。该系统分发
在单个细胞隔间中高效而准确地生产蛋白质
(细胞质)到二十多个部位(膜和隔室)
最终功能住所。通向急诊室的流量由蛋白质控制
蛋白质,但从ER-高尔基连接下游,蛋白质被分类
通过特定的泡囊单独和分批运输
承运人前往承运人所要前往的不同目的地
由特定的飞行员执导。该项目的基本前提是
分拣员和领航员,即交通控制系统的关键要素,
是囊泡载体的完整膜蛋白,并且
识别他们的第一步是孤立和
特定类别的泡状载体的表征。我们建议
使用完整大鼠的肝脏,或灌流的大鼠肝脏或初级
大鼠肝细胞培养作为囊泡载体的方便来源
我们有一个可靠的标志物,聚合的IgA受体,它的形式和
峰值标记时间是每个主要类别的特征
泡状载体。我们最近通过免疫吸附分离出了一种
跨细胞泡囊载体的一部分。我们建议完成ITS
鉴定和重建细胞穿透的最后一步
使用上述组分作为供体的无细胞系统,
受体,包括适当靶点的质膜部分。我们
建议提高针对猪传染性支气管炎整膜蛋白的抗体
并测试它们阻止与目标融合的能力。
同源抗原将作为假定的飞行员进行进一步研究。
抗独特型抗体将作为潜在的工具进行测试
隔离分拣机。我们打算利用胆汁淤积的肝脏
作为末端囊泡缺陷的跨细胞载体的来源
核聚变。我们打算继续进行隔离和定性
在跨高尔基正弦结构域工作的囊泡载体
质膜传递以找出不同或相同的携带者
参与分泌和膜蛋白的运输。既然是这样
工作集中在泡囊载体本身,它将
补充当前关于囊泡所需的胞浆因子的工作
运输。预计这两种方法之间的互动将会取得进展
我们对整个交通控制系统的理解。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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GEORGE E PALADE的其他文献
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{{ truncateString('GEORGE E PALADE', 18)}}的其他基金
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