Hagedorn Elliott J, Yashiro Hanako, Ziel Joshua W, Ihara Shinji, Wang Zheng, Sherwood David R
Department of Biology, Duke University, Science Drive, Box 90388, Durham, NC 27708, USA.
Dev Cell. 2009 Aug;17(2):187-98. doi: 10.1016/j.devcel.2009.06.006.
Integrin expression and activity have been strongly correlated with developmental and pathological processes involving cell invasion through basement membranes. The role of integrins in mediating these invasions, however, remains unclear. Utilizing the genetically and visually accessible model of anchor cell (AC) invasion in C. elegans, we have recently shown that netrin signaling orients a specialized invasive cell membrane domain toward the basement membrane. Here, we demonstrate that the integrin heterodimer INA-1/PAT-3 plays a crucial role in AC invasion, in part by targeting the netrin receptor UNC-40 (DCC) to the AC's plasma membrane. Analyses of the invasive membrane components phosphatidylinositol 4,5-bisphosphate, the Rac GTPase MIG-2, and F-actin further indicate that INA-1/PAT-3 plays a broad role in promoting the plasma membrane association of these molecules. Taken together, these studies reveal a role for integrin in regulating the plasma membrane targeting and netrin-dependent orientation of a specialized invasive membrane domain.
整合素的表达和活性与涉及细胞通过基底膜侵袭的发育和病理过程密切相关。然而，整合素在介导这些侵袭过程中的作用仍不清楚。利用秀丽隐杆线虫中基因和视觉上可及的锚定细胞（AC）侵袭模型，我们最近发现，网蛋白信号将一个特殊的侵袭细胞膜结构域导向基底膜。在此，我们证明整合素异二聚体INA-1/PAT-3在AC侵袭中起关键作用，部分原因是将网蛋白受体UNC-40（DCC）靶向到AC的质膜上。对侵袭性膜成分磷脂酰肌醇4,5-二磷酸、Rac GTP酶MIG-2和F-肌动蛋白的分析进一步表明，INA-1/PAT-3在促进这些分子与质膜的结合方面发挥着广泛作用。综上所述，这些研究揭示了整合素在调节质膜靶向和网蛋白依赖的特殊侵袭膜结构域定向中的作用。
