Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
J Cell Sci. 2009 Dec 1;122(Pt 23):4363-74. doi: 10.1242/jcs.055996. Epub 2009 Nov 10.
Cell adhesion to the extracellular matrix (ECM) is mediated by the integrin family of transmembrane receptors. Integrins link ECM ligands to the cytoskeleton, providing strong attachment to enable cell-shape change and tissue integrity. This connection is made possible by an intracellular complex of proteins, which links to actin filaments and controls signalling cascades that regulate cytoskeletal rearrangements. We have identified stress-fibre-associated focal adhesions that change their composition during tissue morphogenesis. Early expression of alphaPS1betaPS integrin decreases the levels of the actin-nucleating factors Enabled, Diaphanous and profilin, as well as downregulating the amount of F-actin incorporated into the stress fibres. As follicle cells mature in their developmental pathway and become squamous, the integrin in the focal adhesions changes from alphaPS1betaPS to alphaPS2betaPS. During the switch, stress fibres increase their length and change orientation, first changing by 90 degrees and then reorienting back. The normal rapid reorientation requires new expression of alphaPS2betaPS, which also permits recruitment of the adaptor protein tensin. Unexpectedly, it is the extracellular portion of the alphaPS2 subunit that provides the specificity for intracellular recruitment of tensin. Molecular variation of the integrin complex is thus a key component of developmentally programmed morphogenesis.
细胞与细胞外基质（ECM）的黏附是通过整合素家族的跨膜受体介导的。整合素将 ECM 配体与细胞骨架连接起来，提供牢固的附着，使细胞形状发生变化并保持组织完整性。这种连接是通过细胞内的蛋白质复合物实现的，它与肌动蛋白丝相连，并控制信号级联反应，调节细胞骨架的重排。我们已经鉴定出与应力纤维相关的黏着斑，它们在组织形态发生过程中改变其组成。早期表达的α PS1β PS 整合素降低了肌动蛋白成核因子 Enabled、Diaphanous 和 Profilin 的水平，同时下调了整合到应力纤维中的 F-肌动蛋白的量。随着滤泡细胞在其发育途径中成熟并变成鳞状，黏着斑中的整合素从α PS1β PS 转变为α PS2β PS。在转换过程中，应力纤维的长度增加，方向发生变化，首先改变 90 度，然后再重新定向。正常的快速重新定向需要新表达的α PS2β PS，这也允许衔接蛋白 tensin 的募集。出乎意料的是，正是α PS2 亚基的细胞外部分提供了 tensin 细胞内募集的特异性。因此，整合素复合物的分子变异是发育编程形态发生的关键组成部分。
