Role of adherens junction-associated membrane protein shrew-1 in polarized and non-polarized cells in vitro and in vivo

粘附连接相关膜蛋白 Shrew-1 在体外和体内极化和非极化细胞中的作用

• 批准号: 55047701
• 负责人: Professorin Dr. Anna Starzinski-Powitz
• 金额: --
• 依托单位: Institut für Zellbiologie und Neurowissenschaft
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/55047701?language=en
• 关键词: Role; adherens; junction; associated; membrane

Cell migration and invasion of cells into the surrounding tissue are fundamental processes in normal development and pathological conditions. In early development, particularly during neurulation and gastrulation, cells acquire a migratory, mesenchymal phenotype, not unlike that of invasive tumor cells. The invasion of single cells is often correlated with changes in the expression and function of cadherins or immunoglobulin domain-containing cell adhesion molecules and regulatory proteins, e.g. snail family members, transforming growth factor beta. We have discovered a transmembrane protein, shrew-1, which plays a central role in cell migration and invasion. In epithelial cells, shrew-1 localizes to adherens junctions. Its localization and trafficking is responsive to epidermal growth factor (EGF) and scatter factor (SF/HGF) and may mediate the loss of epithelial morphology, increase of migration and invasion and decrease of intercellular adhesion induced by these factors. Shrew-1 may play a role in the morphological plasticity of epithelial cells. We are proposing to extend our studies of the properties of this molecule by computational, bioinformatic analyses, knockdown or overexpression of wildtype or mutant variants of the protein. Cell culture experiments will be complemented by an analysis of shrew-1 function in the development of the mouse mammary gland combining knock-down technology and tissue reconstitution techniques.

细胞迁移和细胞侵入周围组织是正常发育和病理条件下的基本过程。在早期发育中，特别是在神经形成和原肠胚形成期间，细胞获得迁移的间充质表型，与侵袭性肿瘤细胞的表型没有不同。单细胞的侵袭通常与钙粘蛋白或含有免疫球蛋白结构域的细胞粘附分子和调节蛋白（例如snail家族成员、转化生长因子β）的表达和功能的变化相关。我们发现了一种跨膜蛋白shrew-1，它在细胞迁移和侵袭中起着重要作用。在上皮细胞中，shrew-1定位于粘附连接。它的定位和运输对表皮生长因子（EGF）和分散因子（SF/HGF）有反应，并可能介导这些因子引起的上皮形态的丧失、迁移和侵袭的增加以及细胞间粘附的减少。Shrew-1可能在上皮细胞的形态可塑性中发挥作用。我们建议通过计算、生物信息学分析、敲低或过表达野生型或突变型蛋白质变体来扩展我们对该分子性质的研究。细胞培养实验将通过结合敲除技术和组织重建技术分析shrew-1在小鼠乳腺发育中的功能来补充。