{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:18:40Z","timestamp":1790540320562,"version":"4.1.0"},"reference-count":45,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Cyclic stretch is an artificial model of mechanical force loading, which induces the reorientation of vascular endothelial cells (ECs) and their stress fibers in a direction perpendicular to the stretch axis. Rho family GTPases are crucial for cyclic stretch-induced EC reorientation; however, the mechanism underlying stretch-induced activation of Rho family GTPases is unknown. A screen of short-hairpin RNAs targeting 63 Rho-guanine nucleotide exchange factors (Rho-GEFs) revealed that at least 11 Rho-GEFs (Abr, Alsin, ARHGEF10, Bcr, GEF-H1, LARG, p190RhoGEF, PLEKHG1, P-REX2, Solo\/ARHGEF40, and \u03b1-PIX), which specifically or broadly target RhoA, Rac1 and\/or Cdc42, are involved in cyclic stretch-induced perpendicular reorientation of ECs. Overexpression of Solo induced RhoA activation and F-actin accumulation at cell-cell and cell-substrate adhesion sites. Knockdown of Solo suppressed cyclic stretch- or tensile force-induced RhoA activation. Moreover, knockdown of Solo significantly reduced cyclic stretch-induced perpendicular reorientation of ECs when cells were cultured at high density, but not when they were cultured at low density or pretreated with EGTA or VE-cadherin-targeting siRNAs. These results suggest that Solo is involved in cell-cell adhesion-mediated mechanical signal transduction during cyclic stretch-induced EC reorientation.<\/jats:p>","DOI":"10.1242\/jcs.157503","type":"journal-article","created":{"date-parts":[[2015,3,21]],"date-time":"2015-03-21T03:08:04Z","timestamp":1426907284000},"source":"Crossref","is-referenced-by-count":80,"title":["Rho-guanine nucleotide exchange factors involved in cyclic stretch-induced reorientation of vascular endothelial cells"],"prefix":"10.1242","author":[{"given":"Hiyori","family":"Abiko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Hiatari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiya","family":"Mashiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensaku","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2021042613480113200_b01","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.mvr.2008.09.006","article-title":"Small GTPases in mechanosensitive regulation of endothelial barrier.","volume":"77","author":"Birukov","year":"2009","journal-title":"Microvasc. Res."},{"key":"2021042613480113200_b02","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1126\/science.1068999","article-title":"A system for stable expression of short interfering RNAs in mammalian cells.","volume":"296","author":"Brummelkamp","year":"2002","journal-title":"Science"},{"key":"2021042613480113200_b03","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1038\/onc.2013.362","article-title":"Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease.","volume":"33","author":"Cook","year":"2014","journal-title":"Oncogene"},{"key":"2021042613480113200_b04","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1476--4598--3--10","article-title":"Scambio, a novel guanine nucleotide exchange factor for Rho.","volume":"3","author":"Curtis","year":"2004","journal-title":"Mol. Cancer"},{"key":"2021042613480113200_b05","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/j.cub.2004.08.024","article-title":"Developmentally restricted actin-regulatory molecules control morphogenetic cell movements in the zebrafish gastrula.","volume":"14","author":"Daggett","year":"2004","journal-title":"Curr. Biol."},{"key":"2021042613480113200_b06","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/BF01907974","article-title":"Response of cultured endothelial cells to mechanical stimulation.","volume":"84","author":"Dartsch","year":"1989","journal-title":"Basic Res. Cardiol."},{"key":"2021042613480113200_b07","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1126\/science.1162912","article-title":"Stretching single talin rod molecules activates vinculin binding.","volume":"323","author":"del Rio","year":"2009","journal-title":"Science"},{"key":"2021042613480113200_b08","doi-asserted-by":"publisher","first-page":"L141","DOI":"10.1152\/ajplung.00298.2012","article-title":"Rac1 pathway mediates stretch response in pulmonary alveolar epithelial cells.","volume":"305","author":"DiPaolo","year":"2013","journal-title":"Am. J. Physiol."},{"key":"2021042613480113200_b09","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/nrm3112","article-title":"Balancing forces: architectural control of mechanotransduction.","volume":"12","author":"DuFort","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042613480113200_b10","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nature10430","article-title":"Mechanical strain in actin networks regulates FilGAP and integrin binding to filamin A. Nature","volume":"478","author":"Ehrlicher","year":"2011"},{"key":"2021042613480113200_b11","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nature01148","article-title":"Rho GTPases in cell biology.","volume":"420","author":"Etienne-Manneville","year":"2002","journal-title":"Nature"},{"key":"2021042613480113200_b12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ajhg.2013.07.010","article-title":"Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.","volume":"93","author":"Franceschini","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2021042613480113200_b13","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nrm2593","article-title":"Environmental sensing through focal adhesions.","volume":"10","author":"Geiger","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042613480113200_b14","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.1242\/jcs.054866","article-title":"Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding.","volume":"122","author":"Goldyn","year":"2009","journal-title":"J. Cell Sci."},{"key":"2021042613480113200_b15","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nature09198","article-title":"Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics.","volume":"466","author":"Grashoff","year":"2010","journal-title":"Nature"},{"key":"2021042613480113200_b16","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1038\/ncb2254","article-title":"The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins.","volume":"13","author":"Guilluy","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"2021042613480113200_b17","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nrm2596","article-title":"Mechanotransduction in vascular physiology and atherogenesis.","volume":"10","author":"Hahn","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042613480113200_b18","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.febslet.2013.01.043","article-title":"p63RhoGEF-mediated formation of a single polarized lamellipodium is required for chemotactic migration in breast carcinoma cells.","volume":"587","author":"Hayashi","year":"2013","journal-title":"FEBS Lett."},{"key":"2021042613480113200_b19","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1242\/jcs.109447","article-title":"Mechanosensitive systems at the cadherin-F-actin interface.","volume":"126","author":"Huveneers","year":"2013","journal-title":"J. Cell Sci."},{"key":"2021042613480113200_b20","doi-asserted-by":"publisher","first-page":"15895","DOI":"10.1073\/pnas.0506041102","article-title":"Cooperative effects of Rho and mechanical stretch on stress fiber organization.","volume":"102","author":"Kaunas","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021042613480113200_b21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1146\/annurev--cellbio--100109--104027","article-title":"Force generation, transmission, and integration during cell and tissue morphogenesis.","volume":"27","author":"Lecuit","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021042613480113200_b22","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.bbrc.2010.09.046","article-title":"Cyclic stretch-induced stress fiber dynamics \u2013 dependence on strain rate, Rho-kinase and MLCK.","volume":"401","author":"Lee","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042613480113200_b23","doi-asserted-by":"publisher","first-page":"7420","DOI":"10.1021\/bi300758e","article-title":"From mechanical force to RhoA activation.","volume":"51","author":"Lessey","year":"2012","journal-title":"Biochemistry"},{"key":"2021042613480113200_b24","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1083\/jcb.200708194","article-title":"PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility.","volume":"180","author":"Lim","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021042613480113200_b25","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1161\/CIRCRESAHA.107.158329","article-title":"Cadherins, RhoA, and Rac1 are differentially required for stretch-mediated proliferation in endothelial versus smooth muscle cells.","volume":"101","author":"Liu","year":"2007","journal-title":"Circ. Res."},{"key":"2021042613480113200_b26","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1093\/hmg\/ddp582","article-title":"Functional SNP of ARHGEF10 confers risk of atherothrombotic stroke.","volume":"19","author":"Matsushita","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2021042613480113200_b27","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/sj.onc.1201950","article-title":"Pp125FAK is required for stretch dependent morphological response of endothelial cells.","volume":"17","author":"Naruse","year":"1998","journal-title":"Oncogene"},{"key":"2021042613480113200_b28","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1128\/MCB.22.3.774--783.2002","article-title":"Stromal cell-derived factor 1\u03b1 activates LIM kinase 1 and induces cofilin phosphorylation for T-cell chemotaxis.","volume":"22","author":"Nishita","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2021042613480113200_b29","doi-asserted-by":"publisher","first-page":"3577","DOI":"10.1074\/jbc.275.5.3577","article-title":"Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop.","volume":"275","author":"Ohashi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021042613480113200_b30","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1242\/jcs.095794","article-title":"Finding the weakest link: exploring integrin-mediated mechanical molecular pathways.","volume":"125","author":"Roca-Cusachs","year":"2012","journal-title":"J. Cell Sci."},{"key":"2021042613480113200_b31","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nrm1587","article-title":"GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.","volume":"6","author":"Rossman","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042613480113200_b32","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.cell.2006.09.044","article-title":"Force sensing by mechanical extension of the Src family kinase substrate p130Cas.","volume":"127","author":"Sawada","year":"2006","journal-title":"Cell"},{"key":"2021042613480113200_b33","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1101\/gad.1003302","article-title":"Guanine nucleotide exchange factors for Rho GTPases: turning on the switch.","volume":"16","author":"Schmidt","year":"2002","journal-title":"Genes Dev."},{"key":"2021042613480113200_b34","doi-asserted-by":"publisher","first-page":"3051","DOI":"10.1242\/jcs.093716","article-title":"United we stand: integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction.","volume":"125","author":"Schwarz","year":"2012","journal-title":"J. Cell Sci."},{"key":"2021042613480113200_b35","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ceb.2009.05.006","article-title":"Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility.","volume":"21","author":"Tomar","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021042613480113200_b36","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.gene.2005.06.025","article-title":"Identification, expression analysis, genomic organization and cellular location of a novel protein with a RhoGEF domain.","volume":"359","author":"Tse","year":"2005","journal-title":"Gene"},{"key":"2021042613480113200_b37","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1091\/mbc.E10--02--0095","article-title":"Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells.","volume":"21","author":"Tsuji","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"2021042613480113200_b38","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1161\/01.RES.0000200162.94463.d7","article-title":"Role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response.","volume":"98","author":"Tzima","year":"2006","journal-title":"Circ. Res."},{"key":"2021042613480113200_b39","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1038\/nature03952","article-title":"A mechanosensory complex that mediates the endothelial cell response to fluid shear stress.","volume":"437","author":"Tzima","year":"2005","journal-title":"Nature"},{"key":"2021042613480113200_b40","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2174\/1874120701004010129","article-title":"Cyclic force applied to FAs induces actin recruitment depending on the dynamic loading pattern.","volume":"4","author":"Ueki","year":"2010","journal-title":"Open Biomed. Eng. J."},{"key":"2021042613480113200_b41","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1093\/nar\/gkh247","article-title":"Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference.","volume":"32","author":"Ui-Tei","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"2021042613480113200_b42","doi-asserted-by":"publisher","first-page":"130001","DOI":"10.1098\/rsob.130001","article-title":"Actin stress fibre subtypes in mesenchymal-migrating cells.","volume":"3","author":"Vallenius","year":"2013","journal-title":"Open Biol."},{"key":"2021042613480113200_b43","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/nrm2592","article-title":"Mechanotransduction in development: a growing role for contractility.","volume":"10","author":"Wozniak","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021042613480113200_b44","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1006\/bbrc.1996.1057","article-title":"Involvement of rho p21 in cyclic strain-induced tyrosine phosphorylation of focal adhesion kinase (pp125FAK), morphological changes and migration of endothelial cells.","volume":"224","author":"Yano","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021042613480113200_b45","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/ncb2055","article-title":"alpha-Catenin as a tension transducer that induces adherens junction development.","volume":"12","author":"Yonemura","year":"2010","journal-title":"Nat. Cell Biol."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/128\/9\/1683\/1941548\/jcs-128-9-1683.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.157503\/2047194\/jcs157503.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.157503\/2047194\/jcs157503.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T18:12:57Z","timestamp":1621361577000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/doi\/10.1242\/jcs.157503\/259166\/Rho-guanine-nucleotide-exchange-factors-involved"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":45,"URL":"https:\/\/doi.org\/10.1242\/jcs.157503","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1,1]]},"article-number":"jcs.157503"}}