ADAM Proteolytic and Adhesive Function in Cell Migration

描述（由申请人提供）： 亚当斯（一种去整合素和金属蛋白酶）是一类新型的细胞表面糖蛋白，其表现出蛋白水解和粘附活性。亚当斯在生物学环境中的机制，特别是其粘附和蛋白水解结构域之间的相互作用，仍然不清楚。一些证据表明，亚当斯可能在细胞迁移中起作用，如颅神经嵴（CNC）迁移。由于其在面部和头部发育中的重要性，CNC迁移缺陷可能导致颅面缺陷或致命性。据估计，三分之一的人类出生缺陷归因于颅面发育异常。本项目的目标是利用小鼠CNC作为模型系统来探索亚当斯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，并确定亚当斯是否通过其粘附和/或蛋白水解结构域在细胞迁移中起作用。拟议的研究不仅将提供对CNC迁移的进一步了解，而且还将提供一个框架，用于评估亚当斯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。

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.