细胞外基质与一个细胞的肌动蛋白细胞骨架之间的物理联系由被称为“粘着斑”(focal adhesion)的细胞器组成,它们通过“整联蛋白”(或称整合素)发挥作用。它们在人体生理中具有根本性的重要性,因为它们调控细胞粘附、机械传感和控制细胞生长及分化的信号。现在,“粘着斑”的分子架构已通过利用三维超分辨率荧光显微镜在纳米尺度上观测蛋白组织方式而被确定。
它们是组织良好的超级结构,在其中“整联蛋白”和肌动蛋白被一个40纳米长、由部分重叠的蛋白特异性层组成的核分开,又被“人踝蛋白”(talin)系在一起。这种多层架构产生三个或更多单独的腔室,它们调控“粘着斑”的相互独立的功能。本期封面的模型所示为用iPALM(干涉测量光激发定位显微镜)测出的蛋白位置。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi:10.1038/nature09621
Nanoscale architecture of integrin-based cell adhesions
Pakorn Kanchanawong,Gleb Shtengel,Ana M. Pasapera,Ericka B. Ramko,Michael W. Davidson,davidson@magnet.fsu.eduHarald F. Hesshessh@janelia.hhmi.org& Clare M. Waterman
Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing1, 2. Focal adhesions are multifunctional organelles that mediate cell–ECM adhesion, force transmission, cytoskeletal regulation and signalling1, 2, 3. Focal adhesions consist of a complex network4 of trans-plasma-membrane integrins and cytoplasmic proteins that form a?<200-nm plaque5, 6 linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine7, 8. However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photoactivated localization microscopy)9 to map nanoscale protein organization in focal adhesions. Our results reveal that integrins and actin are vertically separated by a ~40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signalling layer containing integrin cytoplasmic tails, focal adhesion kinase and paxillin; an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin, vasodilator-stimulated phosphoprotein and α-actinin. By localizing amino- and carboxy-terminally tagged talins, we reveal talin’s polarized orientation, indicative of a role in organizing the focal adhesion strata. The composite multilaminar protein architecture provides a molecular blueprint for understanding focal adhesion functions.