PMID- 21107430 OWN - NLM STAT- MEDLINE DCOM- 20101202 LR - 20220408 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 468 IP - 7323 DP - 2010 Nov 25 TI - Nanoscale architecture of integrin-based cell adhesions. PG - 580-4 LID - 10.1038/nature09621 [doi] AB - 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 approximately 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 alpha-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. FAU - Kanchanawong, Pakorn AU - Kanchanawong P AD - National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. FAU - Shtengel, Gleb AU - Shtengel G FAU - Pasapera, Ana M AU - Pasapera AM FAU - Ramko, Ericka B AU - Ramko EB FAU - Davidson, Michael W AU - Davidson MW FAU - Hess, Harald F AU - Hess HF FAU - Waterman, Clare M AU - Waterman CM LA - eng GR - Z01 HL005105-01/Intramural NIH HHS/United States GR - Z99 HL999999/Intramural NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Actins) RN - 0 (Integrins) SB - IM CIN - Nat Rev Mol Cell Biol. 2011 Jan;12(1):4. PMID: 21119700 MH - Actins/metabolism MH - Animals MH - Cell Adhesion MH - Cell Line MH - Cell Line, Tumor MH - Cell Membrane/metabolism/ultrastructure MH - Extracellular Matrix/*metabolism/ultrastructure MH - Humans MH - Integrins/*metabolism MH - Mice MH - Models, Biological PMC - PMC3046339 MID - NIHMS255152 EDAT- 2010/11/26 06:00 MHDA- 2010/12/14 06:00 PMCR- 2011/05/25 CRDT- 2010/11/26 06:00 PHST- 2010/03/09 00:00 [received] PHST- 2010/10/28 00:00 [accepted] PHST- 2010/11/26 06:00 [entrez] PHST- 2010/11/26 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] PHST- 2011/05/25 00:00 [pmc-release] AID - nature09621 [pii] AID - 10.1038/nature09621 [doi] PST - ppublish SO - Nature. 2010 Nov 25;468(7323):580-4. doi: 10.1038/nature09621.