Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin
Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin
复制标题
DOI：
10.1083/jcb.200807049
复制
发表时间：
2008-10-06
影响因子：
7.8
通讯作者：
Lehmann, Ruth
中科院分区：
文献类型：
--
作者：
Kunwar, Prabhat S.;Sano, Hiroko;Lehmann, Ruth
尽管在确定控制细胞迁移的指导途径方面取得了重大进展，但细胞如何在完整的生物体中开始移动，获得运动性并与邻近细胞失去联系仍知之甚少。我们发现，在果蝇生殖细胞迁移开始时，内胚层1 （Tre1）中的G蛋白偶联受体（GPCR）的激活指导了G蛋白G β以及粘附连接蛋白和Rho鸟苷三磷酸酶从细胞外围重新分布到生殖细胞的后尾。随后，Tre1活性触发生殖细胞扩散，并引导它们向中肠定向经上皮迁移。向侵袭性迁移的过渡也是转移形成的先决条件，这通常与粘附蛋白的下调有关。我们发现，E-cadherin的均匀下调导致生殖细胞扩散，但在缺乏Tre1的情况下，这不足以促进上皮迁移。因此，我们的发现提示了GPCR功能的新机制，该机制将细胞极性、细胞粘附调节和侵袭联系起来。
Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein-coupled receptor ( GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein G beta as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion.