FUNCTIONS OF BETA 1 INTEGRINS IN GROWTH CONE MOTILITY

Beta 1 整合素在生长锥运动中的功能

• 批准号: 2641684
• 负责人: Christopher S. Stipp
• 金额: $ 3.02万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2641684
• 关键词: SDS polyacrylamide gel electrophoresis; actin binding protein; binding proteins; cell motility; chick embryo; chromophore; developmental neurobiology; fibronectins; growth cones; immunocytochemistry; integrins; laboratory mouse; laminin; lasers; monoclonal antibody; neuronal guidance; neurons; phenotype; protein structure function; statistics /biometry; tissue /cell culture; video microscopy; western blottings

The long term goal of this proposal is to increase our understanding of nervous system development. Such an understanding will be important for the design of treatments for nerve injury and neurological disorders. The experiments will (1) test the hypothesis that beta1 integrins, a major class of receptors for extracellular matrix (ECM), have distinct functions in growth cone motility on the ECM molecules laminin (LN) and (FN) and (2) test for a functional relationship between beta1 integrins and the beta1-binding protein, talin. The experiments will use chromophore assisted laser inactivating (CALl), a unique method that will allow inactivation of beta1 integrins in the growth cone without disrupting beta1 function elsewhere on the cell. Experimental strategy: (1) We will demonstrate that (CALI) can be used to specifically inactivate beta1 integrins. (2) We will use CALI to inactivate beta1 in the filopodia of growth cones of DRG neurons on LN and FN. Changes in filopodial motility will be recorded by time lapse microscopy and analyzed statistically for significance. (3) We will use CALI to inactivate beta1 integrins and talin simultaneously and compare the resulting phenotype to inactivation of beta1 and talin individually. This experiment will be a direct test of the functional relationship between beta1 integrin and talin, a relationship long suspected on the basis of beta1-talin binding and colocalization.

该提议的长期目标是增加我们对 神经系统的发展。这样的理解对于 神经损伤和神经系统疾病治疗的设计。这 实验将（1）检验以下假设：Beta1整合素（主要） 细胞外基质（ECM）的受体类别具有独特的 ECM分子（LN）和 （FN）和（2）测试Beta1整合素之间的功能关系 还有beta1结合蛋白，塔林。实验将使用 发色团辅助激光灭活（呼叫），这是一种独特的方法 允许在没有生长锥中的β1整合素的情况下失活 破坏细胞其他地方的beta1功能。实验策略： （1）我们将证明（cali）可用于专门 灭活β1整合素。 （2）我们将使用cali在 LN和FN上DRG神经元的生长锥的丝状虫。变更 丝虫运动将通过时间衰变显微镜记录，并记录 在统计上分析了重要性。 （3）我们将使用卡利 灭活beta1整合素和塔林同时比较 由beta1和塔林分别失活的表型。这 实验将是对功能关系的直接测试 beta1整合素和塔林，长期以来一直怀疑的关系 beta1-talin结合和共定位。