ADAM Proteolytic and Adhesive Function in Cell Migration

ADAM 在细胞迁移中的蛋白水解和粘附功能

• 批准号: 6884288
• 负责人: LANCE C BRIDGES
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884288
• 关键词: CHO cells; cell adhesion; cell migration; extracellular matrix; gene expression; genetically modified animals; immunofluorescence technique; integrins; laboratory mouse; laminin; membrane proteins; metalloendopeptidases; neural crest; paxillin; point mutation; postdoctoral investigator; protein localization; protein protein interaction; protein structure function; proteolysis; transfection /expression vector; video microscopy

DESCRIPTION (provided by applicant): ADAMs (a disintegrin and a metalloprotease) are a novel class of cell surface glycoproteins that exhibits both proteolytic and adhesive activities. The mechanisms of ADAMs in biological settings, in particular the interplay between their adhesive and proteolytic domains, remain unclear. Several lines of evidence suggest that ADAMs may function in cell migration, such as in cranial neural crest (CNC) migration. Due to their importance in the developing face and head, defects in CNC migration could result in craniofacial defects or lethality. An estimated one-third of human birth defects are attributed to aberrant craniofacial development. The goals of this project are to explore the roles of ADAMs in cell migration utilizing mouse CNC as a model system to establish which integrin(s) and which ADAM(s) participate in mouse CNC migration, and to determine if ADAMs function in cell migration through their adhesive and/or proteolytic domains. The proposed studies will not only provide further insight into CNC migration, but they will provide a framework for evaluating how ADAMs may function in other cell migration events including leukocyte transmigration, angiogenesis, and tumor cell metastasis.

描述(由申请人提供)： ADAMS(一种去整合素和一种金属蛋白酶)是一类新的细胞表面糖蛋白，具有蛋白水解性和粘附性。ADAMS在生物环境中的机制，特别是它们的粘附域和蛋白水解域之间的相互作用，仍然不清楚。一些证据表明，ADAMS可能在细胞迁移中发挥作用，例如在脑神经脊(Cnc)迁移中。由于它们在面部和头部发育中的重要性，数控系统移动中的缺陷可能会导致颅面缺陷或致命性损伤。据估计，三分之一的人类出生缺陷是由于颅面发育异常造成的。本项目的目标是利用小鼠数控系统作为模型系统来探索ADAMS在细胞迁移中的作用，以确定哪个整合素(S)和哪个ADAM(S)参与了小鼠数控系统的迁移，并确定ADAMS是否通过它们的粘附域和/或蛋白水解域在细胞迁移中发挥作用。这些拟议的研究不仅将为进一步深入了解NC迁移提供依据，还将为评估ADAMS如何在其他细胞迁移事件中发挥作用提供一个框架，包括白细胞迁移、血管生成和肿瘤细胞转移。