CAM-1 RTK FUNCTION IN CELL MIGRATION AND CELL POLARITY

CAM-1 RTK 在细胞迁移和细胞极性中的功能

• 批准号: 2881167
• 负责人: WAYNE C FORRESTER
• 金额: $ 17.89万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-22 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2881167
• 关键词: Caenorhabditis elegans; cell migration; cellular polarity; mutant; protein tyrosine kinase

DESCRIPTION (Verbatim from the Applicant's Abstract): Cell migration is critical for metazoan development. In addition to its importance in development, cell migration is an important component of human diseases such as cancer. Metastasis is an active process in which cancerous cells migrate to new sites to form tumors. Metastatic cells utilize many of the same proteins as other migrating cells. The mechanisms by which migrating cells are directed to their proper positions is poorly understood. The long term goal of this project is to understand how migrating cells recognize and respond to the cues that direct their migrations. To investigate cell migration, the principal investigator has identified a Caenorhabditis elegans gene, cam-1, required for cells to migrate to their proper positions. In cam-1 mutants, several migratory cells are shifted anteriorly in their final positions. In addition, the orientation of cell polarity is disrupted. Cam-1 encodes a receptor tyrosine kinase (RTK) related to vertebrate and fly Ror RTKs. Ror proteins are RTKs of unknown function that are expressed in the developing nervous system. Overexpression and loss of cam-1 function result in reciprocal cell migration phenotypes. The data suggest that CAM-1 responds to an anteriorly expressed repulsive cue, a model the experiments in this application are aimed at testing. Cam-1 is expressed in the cells affected in mutants and cam-1 functions autonomously in cells that migrate. The experiments described in this application address the mechanism of CAM-1 function both in cell migration and in cell polarity. To achieve this goal, the principal investigator will take advantage of the simple genetics and morphology offered by C. elegans. Specifically, the principal investigator proposes to address five questions: 1) Do levels or spatial regulation of CAM-1 activity regulate cell migration and orient cell polarity?, 2) What are the extracellular cues that direct migrating cells and orient cell polarity?, 3) Is the kinase domain required for CAM-1 function?, 4) How does CAM-1 transmit its signal? and 5) How does cam-1 interact with the egl-20/Wnt signaling pathway? These experiments will identify new components of the cam-1 pathway and suggest testable models by which CAM-1 may act.

描述（来自申请人摘要的逐字描述）： 对后生动物的发育至关重要除了它的重要性， 细胞迁移是人类疾病的重要组成部分， 癌转移是一个活跃的过程，其中癌细胞迁移到新的 形成肿瘤的部位。转移性细胞利用许多相同的蛋白质， 其他迁移细胞迁移细胞被定向到 人们对它们的适当位置知之甚少。本项目的长期目标 是了解迁移细胞如何识别并响应 引导他们的迁徙。 为了研究细胞迁移，主要研究者已经确定了一种 秀丽隐杆线虫基因cam-1是细胞迁移到其 适当的位置。在cam-1突变体中，几个迁移细胞被移位， 在其最终位置上向前移动。此外，细胞的取向 极性被破坏。Cam-1编码一种受体酪氨酸激酶（RTK）相关的 到脊椎动物和飞行Ror RTK。Ror蛋白是功能未知的RTK， 在发育中的神经系统中表达。过度表达和缺失 CAM-1功能导致相互细胞迁移表型。数据表明 CAM-1对前部表达的排斥性线索做出反应， 本申请中的实验旨在测试。CAM-1表达于 在突变体中受影响的细胞和CAM-1在细胞中自主发挥功能， 迁移。本申请中描述的实验解决了以下机制： CAM-1在细胞迁移和细胞极性中起作用。实现这一 目标，首席研究员将利用简单的遗传学， 形态学由C.优雅的。具体来说，首席研究员 提出了五个问题：1）CAM-1的水平或空间调节 活性调节细胞迁移和定向细胞极性？2)有哪些 细胞外信号引导迁移细胞和定向细胞极性？3)是 CAM-1功能所需的激酶结构域？4)CAM-1如何传输其 信号？5）cam-1与egl-20/Wnt信号通路的相互作用？ 这些实验将确定cam-1通路的新成分，并表明 CAM-1可能发挥作用的可测试模型。