{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:04:17Z","timestamp":1791191057827,"version":"4.1.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organization and function. Here we use electron microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterize the structural organization and signalling pathways associated with nodule formation. Nodules are composed of up to four actin-rich structures linked together by actin bundles. They are enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phosphorylated proteins and are depleted of integrins at the plasma membrane. Nodule formation is dependent on Wiskott\u2013Aldrich syndrome protein (WASp) and the ARP2\/3 complex. WASp<jats:sup>\u2212\/\u2212<\/jats:sup> mouse blood displays impaired platelet aggregate formation at arteriolar shear rates. We propose actin nodules are platelet podosome-related structures required for platelet\u2013platelet interaction and their absence contributes to the bleeding diathesis of Wiskott\u2013Aldrich syndrome.<\/jats:p>","DOI":"10.1038\/ncomms8254","type":"journal-article","created":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T10:13:29Z","timestamp":1433153609000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":108,"title":["Platelet actin nodules are podosome-like structures dependent on Wiskott\u2013Aldrich syndrome protein and ARP2\/3 complex"],"prefix":"10.1038","volume":"6","author":[{"given":"Natalie S.","family":"Poulter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Y.","family":"Pollitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dessislava","family":"Malinova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard B.","family":"Nash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike J.","family":"Hannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Pikramenou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua Z.","family":"Rappoport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Hartwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan M.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-7842","authenticated-orcid":false,"given":"Steven G.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"BFncomms8254_CR1","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1083\/jcb.101.4.1463","volume":"101","author":"J Boyles","year":"1985","unstructured":"Boyles, J., Fox, J. E., Phillips, D. R. & Stenberg, P. E. Organization of the cytoskeleton in resting, discoid platelets: preservation of actin filaments by a modified fixation that prevents osmium damage. J. Cell Biol. 101, 1463\u20131472 (1985).","journal-title":"J. Cell Biol."},{"key":"BFncomms8254_CR2","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1083\/jcb.112.3.407","volume":"112","author":"JH Hartwig","year":"1991","unstructured":"Hartwig, J. H. & DeSisto, M. The cytoskeleton of the resting human blood platelet: structure of the membrane skeleton and its attachment to actin filaments. J. Cell Biol. 112, 407\u2013425 (1991).","journal-title":"J. Cell Biol."},{"key":"BFncomms8254_CR3","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.1084\/jem.20100222","volume":"207","author":"H Falet","year":"2010","unstructured":"Falet, H. et al. A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function. J. Exp. Med. 207, 1967\u20131979 (2010).","journal-title":"J. Exp. Med."},{"key":"BFncomms8254_CR4","doi-asserted-by":"publisher","first-page":"39474","DOI":"10.1074\/jbc.M504672200","volume":"280","author":"OJ McCarty","year":"2005","unstructured":"McCarty, O. J. et al. Rac1 is essential for platelet lamellipodia formation and aggregate stability under flow. J. Biol. Chem. 280, 39474\u201339484 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFncomms8254_CR5","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1182\/blood-2009-12-257212","volume":"115","author":"AY Pollitt","year":"2010","unstructured":"Pollitt, A. Y. et al. Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac. Blood 115, 2938\u20132946 (2010).","journal-title":"Blood"},{"key":"BFncomms8254_CR6","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1182\/blood.V91.8.2645.2645_2645_2657","volume":"91","author":"SJ Shattil","year":"1998","unstructured":"Shattil, S. J., Kashiwagi, H. & Pampori, N. Integrin signaling: the platelet paradigm. Blood 91, 2645\u20132657 (1998).","journal-title":"Blood"},{"key":"BFncomms8254_CR7","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.2174\/138161209787846702","volume":"15","author":"SP Watson","year":"2009","unstructured":"Watson, S. P. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis. Curr. Pharm. Des. 15, 1358\u20131372 (2009).","journal-title":"Curr. Pharm. Des."},{"key":"BFncomms8254_CR8","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1111\/j.1538-7836.2005.01429.x","volume":"3","author":"SP Watson","year":"2005","unstructured":"Watson, S. P., Auger, J. M., McCarty, O. J. & Pearce, A. C. GPVI and integrin alphaIIb beta3 signaling in platelets. J. Thromb. Haemost. 3, 1752\u20131762 (2005).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR9","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1182\/blood-2005-03-1219","volume":"108","author":"S Sabri","year":"2006","unstructured":"Sabri, S. et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment. Blood 108, 134\u2013140 (2006).","journal-title":"Blood"},{"key":"BFncomms8254_CR10","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.1538-7836.2007.02487.x","volume":"5","author":"JE Italiano Jr.","year":"2007","unstructured":"Italiano, J. E. Jr., Patel-Hett, S. & Hartwig, J. H. Mechanics of proplatelet elaboration. J. Thromb. Haemost. 5, (Suppl 1): 18\u201323 (2007).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR11","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1111\/jth.12436","volume":"11","author":"Y Chen","year":"2013","unstructured":"Chen, Y. et al. The abnormal proplatelet formation in MYH9-related macrothrombocytopenia results from an increased actomyosin contractility and is rescued by myosin IIA inhibition. J. Thromb. Haemost. 11, 2163\u20132175 (2013).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR12","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1182\/blood-2012-07-443457","volume":"121","author":"H Schachtner","year":"2013","unstructured":"Schachtner, H. et al. Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane. Blood 121, 2542\u20132552 (2013).","journal-title":"Blood"},{"key":"BFncomms8254_CR13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1083\/jcb.201210090","volume":"200","author":"K Burridge","year":"2013","unstructured":"Burridge, K. & Wittchen, E. S. The tension mounts: stress fibers as force-generating mechanotransducers. J. Cell Biol. 200, 9\u201319 (2013).","journal-title":"J. Cell Biol."},{"key":"BFncomms8254_CR14","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.tcb.2008.03.001","volume":"18","author":"A Lambrechts","year":"2008","unstructured":"Lambrechts, A., Gevaert, K., Cossart, P., Vandekerckhove, J. & Van Troys, M. Listeria comet tails: the actin-based motility machinery at work. Trends Cell Biol. 18, 220\u2013227 (2008).","journal-title":"Trends Cell Biol."},{"key":"BFncomms8254_CR15","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.cell.2011.06.010","volume":"145","author":"AJ Ridley","year":"2011","unstructured":"Ridley, A. J. Life at the leading edge. Cell 145, 1012\u20131022 (2011).","journal-title":"Cell"},{"key":"BFncomms8254_CR16","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/cm.21119","volume":"70","author":"H Schachtner","year":"2013","unstructured":"Schachtner, H., Calaminus, S. D., Thomas, S. G. & Machesky, L. M. Podosomes in adhesion, migration, mechanosensing and matrix remodeling. Cytoskeleton (Hoboken) 70, 572\u2013589 (2013).","journal-title":"Cytoskeleton (Hoboken)"},{"key":"BFncomms8254_CR17","doi-asserted-by":"publisher","first-page":"402","DOI":"10.4161\/cam.5.5.16971","volume":"5","author":"C Yang","year":"2011","unstructured":"Yang, C. & Svitkina, T. Filopodia initiation: focus on the Arp2\/3 complex and formins. Cell Adh. Migr. 5, 402\u2013408 (2011).","journal-title":"Cell Adh. Migr."},{"key":"BFncomms8254_CR18","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0092-8674(04)00456-8","volume":"117","author":"CL de Hoog","year":"2004","unstructured":"de Hoog, C. L., Foster, L. J. & Mann, M. RNA and RNA binding proteins participate in early stages of cell spreading through spreading initiation centers. Cell 117, 649\u2013662 (2004).","journal-title":"Cell"},{"key":"BFncomms8254_CR19","doi-asserted-by":"publisher","first-page":"16782","DOI":"10.1073\/pnas.222652499","volume":"99","author":"H Falet","year":"2002","unstructured":"Falet, H. et al. Importance of free actin filament barbed ends for Arp2\/3 complex function in platelets and fibroblasts. Proc. Natl Acad. Sci. USA 99, 16782\u201316787 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8254_CR20","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1007\/s00424-008-0573-7","volume":"457","author":"I Pleines","year":"2009","unstructured":"Pleines, I. et al. Rac1 is essential for phospholipase C-gamma2 activation in platelets. Pflugers Arch. 457, 1173\u20131185 (2009).","journal-title":"Pflugers Arch."},{"key":"BFncomms8254_CR21","doi-asserted-by":"publisher","first-page":"3364","DOI":"10.1182\/blood-2009-09-242271","volume":"115","author":"I Pleines","year":"2010","unstructured":"Pleines, I. et al. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets. Blood 115, 3364\u20133373 (2010).","journal-title":"Blood"},{"key":"BFncomms8254_CR22","doi-asserted-by":"publisher","first-page":"e22117","DOI":"10.1371\/journal.pone.0022117","volume":"6","author":"H Akbar","year":"2011","unstructured":"Akbar, H. et al. Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation. PLoS ONE 6, e22117 (2011).","journal-title":"PLoS ONE"},{"key":"BFncomms8254_CR23","doi-asserted-by":"publisher","first-page":"e54663","DOI":"10.1371\/journal.pone.0054663","volume":"8","author":"R Goggs","year":"2013","unstructured":"Goggs, R., Savage, J. S., Mellor, H. & Poole, A. W. The small GTPase Rif is dispensable for platelet filopodia generation in mice. PLoS ONE 8, e54663 (2013).","journal-title":"PLoS ONE"},{"key":"BFncomms8254_CR24","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1111\/j.1538-7836.2008.03141.x","volume":"6","author":"SD Calaminus","year":"2008","unstructured":"Calaminus, S. D., Thomas, S., McCarty, O. J., Machesky, L. M. & Watson, S. P. Identification of a novel, actin-rich structure, the actin nodule, in the early stages of platelet spreading. J. Thromb. Haemost. 6, 1944\u20131952 (2008).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR25","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1242\/jcs.02390","volume":"118","author":"S Linder","year":"2005","unstructured":"Linder, S. & Kopp, P. Podosomes at a glance. J. Cell Sci. 118, 2079\u20132082 (2005).","journal-title":"J. Cell Sci."},{"key":"BFncomms8254_CR26","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1146\/annurev.immunol.17.1.905","volume":"17","author":"SB Snapper","year":"1999","unstructured":"Snapper, S. B. & Rosen, F. S. The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization. Annu. Rev. Immunol. 17, 905\u2013929 (1999).","journal-title":"Annu. Rev. Immunol."},{"key":"BFncomms8254_CR27","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1111\/imr.12114","volume":"256","author":"DA Moulding","year":"2013","unstructured":"Moulding, D. A., Record, J., Malinova, D. & Thrasher, A. J. Actin cytoskeletal defects in immunodeficiency. Immunol. Rev. 256, 282\u2013299 (2013).","journal-title":"Immunol. Rev."},{"key":"BFncomms8254_CR28","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S1074-7613(00)80590-7","volume":"9","author":"SB Snapper","year":"1998","unstructured":"Snapper, S. B. et al. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Immunity 9, 81\u201391 (1998).","journal-title":"Immunity"},{"key":"BFncomms8254_CR29","doi-asserted-by":"crossref","first-page":"4166","DOI":"10.1182\/blood.V94.12.4166","volume":"94","author":"BS Gross","year":"1999","unstructured":"Gross, B. S. et al. Regulation and function of WASp in platelets by the collagen receptor, glycoprotein VI. Blood 94, 4166\u20134176 (1999).","journal-title":"Blood"},{"key":"BFncomms8254_CR30","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1365-2141.2007.06745.x","volume":"139","author":"MI Lutskiy","year":"2007","unstructured":"Lutskiy, M. I., Shcherbina, A., Bachli, E. T., Cooley, J. & Remold-O'Donnell, E. WASP localizes to the membrane skeleton of platelets. Br. J. Haematol. 139, 98\u2013105 (2007).","journal-title":"Br. J. Haematol."},{"key":"BFncomms8254_CR31","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/j.1365-2141.2009.07959.x","volume":"148","author":"A Shcherbina","year":"2010","unstructured":"Shcherbina, A. et al. WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling. Br. J. Haematol. 148, 416\u2013427 (2010).","journal-title":"Br. J. Haematol."},{"key":"BFncomms8254_CR32","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/sj.embor.7400665","volume":"7","author":"S Tsuboi","year":"2006","unstructured":"Tsuboi, S., Nonoyama, S. & Ochs, H. D. Wiskott-Aldrich syndrome protein is involved in alphaIIb beta3-mediated cell adhesion. EMBO Rep. 7, 506\u2013511 (2006).","journal-title":"EMBO Rep."},{"key":"BFncomms8254_CR33","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1366\/11-06398","volume":"65","author":"BO Leung","year":"2011","unstructured":"Leung, B. O. & Chou, K. C. Review of super-resolution fluorescence microscopy for biology. Appl. Spectrosc. 65, 967\u2013980 (2011).","journal-title":"Appl. Spectrosc."},{"key":"BFncomms8254_CR34","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1002\/jbio.200900089","volume":"3","author":"DM Owen","year":"2010","unstructured":"Owen, D. M. et al. PALM imaging and cluster analysis of protein heterogeneity at the cell surface. J. Biophotonics 3, 446\u2013454 (2010).","journal-title":"J. Biophotonics"},{"key":"BFncomms8254_CR35","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nmeth.1220","volume":"5","author":"J Riedl","year":"2008","unstructured":"Riedl, J. et al. Lifeact: a versatile marker to visualize F-actin. Nat. Methods 5, 605\u2013607 (2008).","journal-title":"Nat. Methods"},{"key":"BFncomms8254_CR36","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/cm.21160","volume":"71","author":"MG Lemieux","year":"2014","unstructured":"Lemieux, M. G. et al. Visualization of the actin cytoskeleton: Different F-actin-binding probes tell different stories. Cytoskeleton 71, 157\u2013169 (2014).","journal-title":"Cytoskeleton"},{"key":"BFncomms8254_CR37","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.ejcb.2012.04.002","volume":"91","author":"H Schachtner","year":"2012","unstructured":"Schachtner, H. et al. Tissue inducible Lifeact expression allows visualization of actin dynamics in vivo and ex vivo. Eur. J. Cell Biol. 91, 923\u2013929 (2012).","journal-title":"Eur. J. Cell Biol."},{"key":"BFncomms8254_CR38","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1242\/jcs.056218","volume":"123","author":"AL Mattheyses","year":"2010","unstructured":"Mattheyses, A. L., Simon, S. M. & Rappoport, J. Z. Imaging with total internal reflection fluorescence microscopy for the cell biologist. J. Cell Sci. 123, 3621\u20133628 (2010).","journal-title":"J. Cell Sci."},{"key":"BFncomms8254_CR39","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1146\/annurev.bb.13.060184.001335","volume":"13","author":"D Axelrod","year":"1984","unstructured":"Axelrod, D., Burghardt, T. P. & Thompson, N. L. Total internal reflection fluorescence. Annu. Rev. Biophys. Bioeng. 13, 247\u2013268 (1984).","journal-title":"Annu. Rev. Biophys. Bioeng."},{"key":"BFncomms8254_CR40","doi-asserted-by":"publisher","first-page":"a004994","DOI":"10.1101\/cshperspect.a004994","volume":"3","author":"ID Campbell","year":"2011","unstructured":"Campbell, I. D. & Humphries, M. J. Integrin structure, activation, and interactions. Cold Spring Harb. Perspect. Biol. 3, a004994 (2011).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"BFncomms8254_CR41","doi-asserted-by":"publisher","first-page":"15738","DOI":"10.1073\/pnas.0904346106","volume":"106","author":"MP Blundell","year":"2009","unstructured":"Blundell, M. P. et al. Phosphorylation of WASp is a key regulator of activity and stability in vivo. Proc. Natl Acad. Sci. USA 106, 15738\u201315743 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8254_CR42","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1073\/pnas.0610275104","volume":"104","author":"MA de la Fuente","year":"2007","unstructured":"de la Fuente, M. A. et al. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP). Proc. Natl Acad. Sci. USA 104, 926\u2013931 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms8254_CR43","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1007\/s10038-003-0083-6","volume":"48","author":"N Andreu","year":"2003","unstructured":"Andreu, N. et al. Identification and characterization of a novel splice-site mutation in a patient with Wiskott-Aldrich syndrome. J. Hum. Genet. 48, 590\u2013593 (2003).","journal-title":"J. Hum. Genet."},{"key":"BFncomms8254_CR44","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.4049\/jimmunol.175.2.1329","volume":"175","author":"MI Lutskiy","year":"2005","unstructured":"Lutskiy, M. I., Rosen, F. S. & Remold-O'Donnell, E. Genotype-proteotype linkage in the Wiskott-Aldrich syndrome. J. Immunol. 175, 1329\u20131336 (2005).","journal-title":"J. Immunol."},{"key":"BFncomms8254_CR45","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/nmeth.1812","volume":"9","author":"S Cox","year":"2012","unstructured":"Cox, S. et al. Bayesian localization microscopy reveals nanoscale podosome dynamics. Nat. Method 9, 195\u2013200 (2012).","journal-title":"Nat. Method"},{"key":"BFncomms8254_CR46","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1091\/mbc.e12-12-0856","volume":"24","author":"K van den Dries","year":"2013","unstructured":"van den Dries, K. et al. Dual-color superresolution microscopy reveals nanoscale organization of mechanosensory podosomes. Mol. Biol. Cell 24, 2112\u20132123 (2013).","journal-title":"Mol. Biol. Cell"},{"key":"BFncomms8254_CR47","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1034\/j.1600-065X.2002.18906.x","volume":"189","author":"J Delon","year":"2002","unstructured":"Delon, J., Stoll, S. & Germain, R. N. Imaging of T-cell interactions with antigen presenting cells in culture and in intact lymphoid tissue. Immunol. Rev. 189, 51\u201363 (2002).","journal-title":"Immunol. Rev."},{"key":"BFncomms8254_CR48","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1016\/j.jbiomech.2007.04.006","volume":"40","author":"SE Lee","year":"2007","unstructured":"Lee, S. E., Kamm, R. D. & Mofrad, M. R. Force-induced activation of talin and its possible role in focal adhesion mechanotransduction. J. Biomech. 40, 2096\u20132106 (2007).","journal-title":"J. Biomech."},{"key":"BFncomms8254_CR49","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1529\/biophysj.107.108472","volume":"94","author":"CT Mierke","year":"2008","unstructured":"Mierke, C. T. et al. Mechano-coupling and regulation of contractility by the vinculin tail domain. Biophys. J. 94, 661\u2013670 (2008).","journal-title":"Biophys. J."},{"key":"BFncomms8254_CR50","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nrm3624","volume":"14","author":"DA Calderwood","year":"2013","unstructured":"Calderwood, D. A., Campbell, I. D. & Critchley, D. R. Talins and kindlins: partners in integrin-mediated adhesion. Nat. Rev. Mol. Cell Biol. 14, 503\u2013517 (2013).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFncomms8254_CR51","doi-asserted-by":"publisher","first-page":"3103","DOI":"10.1084\/jem.20071800","volume":"204","author":"BG Petrich","year":"2007","unstructured":"Petrich, B. G. et al. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J. Exp. Med. 204, 3103\u20133111 (2007).","journal-title":"J. Exp. Med."},{"key":"BFncomms8254_CR52","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.tcb.2006.07.004","volume":"16","author":"WH Ziegler","year":"2006","unstructured":"Ziegler, W. H., Liddington, R. C. & Critchley, D. R. The structure and regulation of vinculin. Trends Cell Biol. 16, 453\u2013460 (2006).","journal-title":"Trends Cell Biol."},{"key":"BFncomms8254_CR53","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1083\/jcb.200703036","volume":"179","author":"JD Humphries","year":"2007","unstructured":"Humphries, J. D. et al. Vinculin controls focal adhesion formation by direct interactions with talin and actin. J. Cell Biol. 179, 1043\u20131057 (2007).","journal-title":"J. Cell Biol."},{"key":"BFncomms8254_CR54","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1111\/j.1538-7836.2010.03998.x","volume":"8","author":"JV Mitsios","year":"2010","unstructured":"Mitsios, J. V. et al. What is vinculin needed for in platelets? J. Thromb. Haemost. 8, 2294\u20132304 (2010).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR55","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.ceb.2011.04.011","volume":"23","author":"AL Neisch","year":"2011","unstructured":"Neisch, A. L. & Fehon, R. G. Ezrin, Radixin and Moesin: key regulators of membrane-cortex interactions and signaling. Curr. Opin. Cell Biol. 23, 377\u2013382 (2011).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFncomms8254_CR56","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1182\/blood-2009-10-246751","volume":"117","author":"S Tadokoro","year":"2011","unstructured":"Tadokoro, S. et al. A potential role for alpha-actinin in inside-out alphaIIbbeta3 signaling. Blood 117, 250\u2013258 (2011).","journal-title":"Blood"},{"key":"BFncomms8254_CR57","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1038\/ncomms2402","volume":"4","author":"K van den Dries","year":"2013","unstructured":"van den Dries, K. et al. Interplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations. Nat. Commun. 4, 1412 (2013).","journal-title":"Nat. Commun."},{"key":"BFncomms8254_CR58","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1161\/ATVBAHA.108.167296","volume":"28","author":"JM Auger","year":"2008","unstructured":"Auger, J. M. & Watson, S. P. Dynamic tyrosine kinase-regulated signaling and actin polymerization mediate aggregate stability under shear. Arterioscler. Thromb. Vasc. Biol. 28, 1499\u20131504 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"BFncomms8254_CR59","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/j.1538-7836.2007.02377.x","volume":"5","author":"SD Calaminus","year":"2007","unstructured":"Calaminus, S. D. et al. A major role for Scar\/WAVE-1 downstream of GPVI in platelets. J. Thromb. Haemost. 5, 535\u2013541 (2007).","journal-title":"J. Thromb. Haemost."},{"key":"BFncomms8254_CR60","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/nmeth0310-168","volume":"7","author":"J Riedl","year":"2010","unstructured":"Riedl, J. et al. Lifeact mice for studying F-actin dynamics. Nat. Meth 7, 168\u2013169 (2010).","journal-title":"Nat. Meth"},{"key":"BFncomms8254_CR61","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1038\/nature08231","volume":"460","author":"BJ Nolen","year":"2009","unstructured":"Nolen, B. J. et al. Characterization of two classes of small molecule inhibitors of Arp2\/3 complex. Nature 460, 1031\u20131034 (2009).","journal-title":"Nature"},{"key":"BFncomms8254_CR62","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.chembiol.2013.03.019","volume":"20","author":"B Hetrick","year":"2013","unstructured":"Hetrick, B., Han, M. S., Helgeson, L. A. & Nolen, B. J. Small molecules CK-666 and CK-869 inhibit actin-related protein 2\/3 complex by blocking an activating conformational change. Chem. Biol. 20, 701\u2013712 (2013).","journal-title":"Chem. Biol."},{"key":"BFncomms8254_CR63","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1038\/nmeth.1768","volume":"8","author":"GT Dempsey","year":"2011","unstructured":"Dempsey, G. T., Vaughan, J. C., Chen, K. H., Bates, M. & Zhuang, X. Evaluation of fluorophores for optimal performance in localization-based super-resolution imaging. Nat. Methods 8, 1027\u20131036 (2011).","journal-title":"Nat. Methods"},{"key":"BFncomms8254_CR64","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1126\/science.1127344","volume":"313","author":"E Betzig","year":"2006","unstructured":"Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642\u20131645 (2006).","journal-title":"Science"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms8254.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8254","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms8254.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T11:33:00Z","timestamp":1672918380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms8254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,1]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,11,3]]}},"alternative-id":["BFncomms8254"],"URL":"https:\/\/doi.org\/10.1038\/ncomms8254","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,1]]},"assertion":[{"value":"17 December 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7254"}}