Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M139PT, UK.
Nat Cell Biol. 2013 Jan;15(1):17-27. doi: 10.1038/ncb2646.
The extracellular matrix has a crucial role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues; however, the underlying mechanisms remain elusive. By using Cre–Lox deletion we show that β1 integrins are required for normal mammary gland morphogenesis and lumen formation, both in vivo and in a three-dimensional primary culture model in which epithelial cells directly contact a basement membrane. Downstream of basement membrane β1 integrins, Rac1 is not involved; however, ILK is needed to polarize microtubule plus ends at the basolateral membrane and disrupting each of these components prevents lumen formation. The integrin–microtubule axis is necessary for the endocytic removal of apical proteins from the basement-membrane–cell interface and for internal Golgi positioning. We propose that this integrin signalling network controls the delivery of apical components to the correct surface and thereby governs the orientation of polarity and development of lumens.
细胞外基质在决定上皮极性的空间方位和腺组织中腔的形成方面起着关键作用；然而，其潜在的机制仍不清楚。通过使用 Cre-Lox 删除，我们表明β1 整合素对于正常乳腺形态发生和管腔形成是必需的，无论是在体内还是在三维原代培养模型中，其中上皮细胞直接与基底膜接触。在基底膜β1 整合素的下游，Rac1 不参与；然而，ILK 用于将微管的正极在基底外侧膜上极化，并且破坏这些成分中的每一个都防止腔形成。整合素-微管轴对于从基底膜-细胞界面处的顶端蛋白的内吞去除以及内部高尔基体定位是必需的。我们提出，这个整合素信号网络控制顶端成分递送到正确的表面，从而控制极性的方向和腔的发育。
