细胞黏附与迁移是细胞基本的生命活动，该过程依赖细胞黏附分子-整合素在活化和去活化状态间的动态转换。目前对于整合素的研究大多集中在其活化机制上，关于整合素的去活化机制研究非常有限。本项目将研究并揭示一种低密度脂蛋白受体相关蛋白（LRP12）介导的整合素去活化的全新机制。我们前期研究已经发现LRP12可与整合素α4β1特异性结合并抑制整合素活化，可能作为一种全新的蛋白参与整合素的去活化调控。在本项目中，我们将进一步研究LRP12-α4β1相互作用的分子基础；揭示LRP12抑制α4β1活化的分子机制并探究其下游信号通路；同时在迁移细胞中检测LRP12、活化和非活化α4β1的亚细胞定位及相互关系，研究LRP12在细胞迁移过程中的作用。以上研究将揭示LRP12调控α4β1整合素去活化的全新机制，并阐明其在细胞黏附与迁移过程中的生物学功能。

Cell adhesion and migration are essential cell behaviors, which are dependent on the dynamic transformation of cell adhesion molecular-integrin activation and inactivation. However, most studies focus on the molecular mechanism of integrin activation at present. The mechanism of integrin inactivation is still obscure. Herein, we investigate a novel mechanism of low density lipoprotein receptor-related protein 12 (LRP12) mediated integrin inactivation. Our preliminary study has found that LRP12 associates with integrin α4β1 and specifically inhibits integrin activation, which might be a new protein in regulating integrin inactivation. In this project, we will further investigate LRP12-α4β1 interaction and try to discover the molecular mechanism of LRP12-mediated inactivation of integrin α4β1 and the downstream signaling. In migrating cells, we will investigate the subcellular localization of LRP12, activated and inactivated α4β1 integrin and their relationship to study the function of LRP12 on cell migration. Our findings will reveal a novel mechanism of LRP12-mediated α4β1 integrin inactivation, and illuminate the biological function in regulating cell adhesion and migration.