CELL SECRETION AND MEMBRANE FORMATION IN THE PANCREAS

胰腺中的细胞分泌和膜形成

基本信息

批准号：
3225735
负责人：
JAMES Douglas JAMIESON
金额：
$ 21.16万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-08-01 至 1987-07-31
项目状态：
已结题

项目摘要

The long -range goal of this proposal is to continue to examine the functional and biochemical properties of the apical and basolateral plasmlemmal domains of the rat pancreatic acinar cell as they relate to stimulus-secretion coupling in a polarized glandular epithelial cell, and to define the factors involved in generation and maintenance of an organized epithelium both in the embryonic pancreas and in a rat acinar cell tumor. First, we plan to isolate and characterize biochemically the apical and basolateral plasmalemmal domains of the adult rat acinar cell preparatory to raising monoclonal antibodies for use in studies of apical/basolateral membrane biogenesis. Studies are also planned to characterize the topologic distribution and biochemical properties of the CCK receptor as an example of a specific basolateral membrane protein using autoradiography and affinity labeling with 125 I-labeled CCK-8 receptor probes. Second, we propose to characterize, using biochemical and immunochemical techniques, the properties of developmentally regulated plasmalemmal proteins that may be involved in cell-cell and cell-substratum interaction that accompany establishment of a polarized, functional epithelium in the embryonic rat pancreas including ontogeny of CCK receptors. Finally, using a transplantable rat acinar cell tumor whose cells reorganize into polarized epithelia in association with deposition of basal lamina when in contact with mesenchymally-derived tissues in vivo, we plan to examine directly in vitro the role of basal lamina and its components in establishment and maintenance of polarized epithelial structures and in regulatin of cell growth. These studies should further our understanding of the mechanisms wherein basal lamina mediates epithelial-mesenchymal interactions required for genesis of normal tissue architecture during pancreatic development and in the future may help in understanding potential aberrations of this interaction that may underly neoplastic transformation and developmental abnormalities.

该提案的长期目标是继续审查顶端和基底外侧的功能和生化特性大鼠胰腺腺泡细胞的质膜结构域，因为它们与极化腺上皮细胞中的刺激-分泌耦合，以及定义涉及生成和维护的因素胚胎胰腺和大鼠腺泡中的组织化上皮细胞肿瘤。首先，我们计划分离并表征生化成年大鼠腺泡细胞的顶端和基底外侧质膜结构域准备生产单克隆抗体用于研究顶/基底外侧膜生物发生。还计划进行研究表征拓扑分布和生化特性 CCK 受体作为特定基底外侧膜蛋白的示例，使用放射自显影和 125 I 标记的 CCK-8 受体亲和标记探针。其次，我们建议使用生化和免疫化学技术，发育调节的特性可能参与细胞间和细胞基质的质膜蛋白伴随着极化的、功能性的建立的相互作用胚胎大鼠胰腺上皮，包括 CCK 的个体发育受体。最后，使用可移植的大鼠腺泡细胞肿瘤，其细胞重组为极化上皮，与沉积相关当基底层与体内的间充质衍生组织接触时，我们计划直接在体外检查基底层及其作用极化上皮细胞建立和维持的组成部分结构和细胞生长的调节。这些研究应该进一步我们对基底层介导机制的理解正常组织发生所需的上皮-间质相互作用胰腺发育期间和未来的结构可能有助于了解这种相互作用的潜在畸变可能是肿瘤转化和发育异常。