Nanoscale architecture of integrin-based cell adhesions
By Pakorn Kanchanawong, G. Shtengel, A. M. Pasapera, Ericka B. Ramko, Michael W. Davidson, H. Hess, Clare M. Waterman. Nature, 2010
1,535 citations recorded by the source corpus.
Cell adhesions to the extracellular matrix (ECM) are necessary for morphogenesis, immunity and wound healing. Focal adhesions are multifunctional organelles that mediate cell–ECM adhesion, force transmission, cytoskeletal regulation and signalling. Focal adhesions consist of a complex network of trans-plasma-membrane integrins and cytoplasmic proteins that form a <200-nm plaque linking the ECM to the actin cytoskeleton. The complexity of focal adhesion composition and dynamics implicate an intricate molecular machine. However, focal adhesion molecular architecture remains unknown. Here we used three-dimensional super-resolution fluorescence microscopy (interferometric photoactivated localization microscopy) 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.
Subfields: Atomic and Molecular Physics, and Optics, Cell Biology, Immunology and Allergy
View Paper: https://www.semanticscholar.org/paper/939a53d2bbc32e3f3426ebda97bd69e8065d775c
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Citations in the corpus
- Integrin-mediated mechanotransduction (2016, background): “…is followed by the integrin signaling module containing THD, FAK, and paxillin within 20 nm of the plasma membrane, and then a force transduction module containing the talin rod domain, vinculin, and the VASP–zyxin complex that are connected to F-actin (Hu et al., 2007; Kanchanawong et al., 2010).”
- Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. (2014, background): “inhibits axonal growth and healing [18], but promotes astrocyte attachment as a”
- Actin dynamics, architecture, and mechanics in cell motility. (2014, background): “How ventral stress fibers are nucleated is not completely known, but seems to involve formins and Ena/VASP proteins and possibly Arp2/3 complex networks as well (143, 315).”