MOLECULAR/CELLULAR ACTION OF CRANIN IN NEURAL CELLS

神经细胞中颅蛋白的分子/细胞作用

• 批准号: 3477345
• 负责人: NEIL R SMALHEISER
• 金额: $ 9.9万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477345
• 关键词: axon; binding proteins; cell cell interaction; central nervous system; chick embryo; complementary DNA; developmental neurobiology; extracellular matrix; laboratory mouse; laboratory rabbit; laminin; membrane activity; membrane proteins; molecular cloning; monoclonal antibody; nervous system regeneration; neurogenesis; neuronal guidance; protein sequence; protein structure function; transfection

the extracullular matrix protein laminin is extremely potent in stimulating and guiding the growth of axons. Moreover, it is expressed in the developing and regenerating brain, in parallel with active axonal outgrowth. The effects of laminin may be clinically important in promoting recovery following brain insults, because exogenous grafts containing laminin coated surfacts can permit regeneration of axons to occur within the central nervous system of adult mammals. Neural cells interact with laminin via cell surface molecules. The first step in understanding how laminin's neurite printing effects can be regulated or facilitated is to learn the identities and roles of the laminin-binding proteins found on neural cell surfaces. This proposal tests the hypothesis that a newly discovered laminin-binding protein, cranin, is critical in mediating some of laminin's actions on neural cells. Antibodies will bs raised against cranin that block its binding to laminin. Neural cells will be exposed to these antibodies to test whether their behavioral responses to laminin will be altered. These or other anti-cranin antibodies will also be alloyed to describe the pattern of cranin's expression in developing and regenerating brain, and to examine possible structural modifications of cranin that occur as a function of developmental stags, types of tissue, or under different physiologic conditions. the binding of cranin to laminin will also be examined, for example to test whether cranin binds to a domain of laminin with known neurite promoting activity or other#r bioactivities. Thus. a broad body of both direct and correlative evidence will be adduced to suggest the nature of cranin's roles in neural cells. The molecular cloning of cranin will be completed. This will allow its amino acid sequence and other detailed structural features to be deduce. Furthermore, cranin deficient cells will be transfected with cranin cDNA and assayed for new responsiveness to laminin. This will provides a conclusive test of cranin's proposed role as a laminin 'receptor'. Cranin may be critical in regulating the ability of axons to extend or regenerate under certain conditions, hence it is important to understand cranin's structure and function. Information gained via cloning may lead to news means of controlling the expression of cranin in brain, and thus promote optimal axonal growth both in the fetus and in the adult human following insults.

细胞外基质蛋白层粘连蛋白在 刺激和引导轴突的生长。 而且是 在发育和再生的大脑中表达， 轴突生长活跃 层粘连蛋白的作用可能是 在促进脑损伤后的恢复方面具有临床重要性， 因为含有层粘连蛋白包被的表面的外源性移植物可以 允许轴突再生发生在中枢神经系统内 成年哺乳动物系统。 神经细胞通过细胞表面分子与层粘连蛋白相互作用。的 了解层粘连蛋白的神经突印刷作用的第一步 是学习身份， 神经细胞核层粘连蛋白结合蛋白的作用 表面。 这一提议验证了一个假设，即一个新的 发现的层粘连蛋白结合蛋白cranin在 介导层粘连蛋白对神经细胞的某些作用。 针对cranin的抗体会产生，从而阻止cranin与 层粘连蛋白。 神经细胞将接触这些抗体进行测试 他们对层粘连蛋白的行为反应是否会改变。 这些或其他抗cranin抗体也将与 描述cranin在发育过程中的表达模式， 再生大脑，并检查可能的结构 作为发育的函数发生的cranin的修饰 鹿、组织类型或在不同的生理条件下。 例如，还将检查cranin与层粘连蛋白的结合 为了测试cranin是否与层粘连蛋白的结构域结合， 神经突促进活性或其它生物活性。 就这样。广泛 直接和相关证据的主体将被援引， 表明了cranin在神经细胞中的作用。 克兰宁的分子克隆即将完成。 这将允许 它的氨基酸序列和其他详细的结构特征， 是演绎。 此外，将转染cranin缺陷细胞， 与cranin cDNA，并测定新的层粘连蛋白的反应性。 这将提供一个结论性的测试克拉宁的拟议作用， 层粘连蛋白“受体”。 Cranin可能是关键，在调节 轴突在一定条件下延伸或再生的能力， 因此，了解cranin结构， 功能 通过克隆获得的信息可能导致新闻手段 控制脑中cranin的表达，从而促进 在胎儿和成人中的最佳轴突生长 在侮辱之后。