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: 7076168
• 负责人: LANCE C BRIDGES
• 金额: $ 0.7万
• 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 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7076168
• 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）： ADAM（解整合素和金属蛋白酶）是一类新型细胞表面糖蛋白，具有蛋白水解和粘附活性。 ADAM 在生物环境中的机制，特别是其粘附域和蛋白水解域之间的相互作用，仍不清楚。多项证据表明 ADAM 可能在细胞迁移中发挥作用，例如在颅神经嵴 (CNC) 迁移中。由于其在面部和头部发育中的重要性，CNC 迁移中的缺陷可能会导致颅面缺陷或致命。据估计，人类出生缺陷的三分之一归因于颅面发育异常。该项目的目标是利用小鼠 CNC 作为模型系统来探索 ADAM 在细胞迁移中的作用，以确定哪些整合素和哪些 ADAM 参与小鼠 CNC 迁移，并确定 ADAM 是否通过其粘附和/或蛋白水解域在细胞迁移中发挥作用。拟议的研究不仅将进一步深入了解 CNC 迁移，还将提供一个框架来评估 ADAM 如何在其他细胞迁移事件中发挥作用，包括白细胞迁移、血管生成和肿瘤细胞转移。