細(xì)胞外基質(zhì)與一個(gè)細(xì)胞的肌動(dòng)蛋白細(xì)胞骨架之間的物理聯(lián)系由被稱為“粘著斑”(focal adhesion)的細(xì)胞器組成,,它們通過(guò)“整聯(lián)蛋白”(或稱整合素)發(fā)揮作用,。它們?cè)谌梭w生理中具有根本性的重要性,因?yàn)樗鼈冋{(diào)控細(xì)胞粘附,、機(jī)械傳感和控制細(xì)胞生長(zhǎng)及分化的信號(hào)。現(xiàn)在,,“粘著斑”的分子架構(gòu)已通過(guò)利用三維超分辨率熒光顯微鏡在納米尺度上觀測(cè)蛋白組織方式而被確定,。
它們是組織良好的超級(jí)結(jié)構(gòu),在其中“整聯(lián)蛋白”和肌動(dòng)蛋白被一個(gè)40納米長(zhǎng),、由部分重疊的蛋白特異性層組成的核分開(kāi),,又被“人踝蛋白”(talin)系在一起。這種多層架構(gòu)產(chǎn)生三個(gè)或更多單獨(dú)的腔室,,它們調(diào)控“粘著斑”的相互獨(dú)立的功能,。本期封面的模型所示為用iPALM(干涉測(cè)量光激發(fā)定位顯微鏡)測(cè)出的蛋白位置。(生物谷Bioon.com)
生物谷推薦英文摘要:
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,[email protected] F. [email protected]& 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.