ADAM Proteolytic and Adhesive Function in Cell Migration

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。

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.