{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:58:40Z","timestamp":1769597920547,"version":"3.49.0"},"reference-count":65,"publisher":"American Society for Cell Biology (ASCB)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>The apical brush border membrane (BBM) of intestinal epithelial cells forms a highly structured and dynamic environmental interface that serves to regulate cellular physiology and block invasion by intestinal microbes and their products. How the BBM dynamically responds to pathogenic and commensal bacterial signals can define intestinal homeostasis and immune function. We previously found that in model intestinal epithelium, the conversion of apical membrane sphingomyelin to ceramide by exogenous bacterial sphingomyelinase (SMase) protected against the endocytosis and toxicity of cholera toxin. Here we elucidate a mechanism of action by showing that SMase induces a dramatic, reversible, RhoA-dependent alteration of the apical cortical F-actin network. Accumulation of apical membrane ceramide is necessary and sufficient to induce the actin phenotype, and this coincides with altered membrane structure and augmented innate immune function as evidenced by resistance to invasion by Salmonella.<\/jats:p>","DOI":"10.1091\/mbc.e15-05-0293","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T04:28:32Z","timestamp":1455164912000},"page":"1120-1130","source":"Crossref","is-referenced-by-count":5,"title":["Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion"],"prefix":"10.1091","volume":"27","author":[{"given":"David E.","family":"Saslowsky","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Digestive Diseases Center, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay R.","family":"Thiagarajah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Digestive Diseases Center, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth A.","family":"McCormick","sequence":"additional","affiliation":[{"name":"Harvard Digestive Diseases Center, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02115"},{"name":"Division of Infectious Diseases, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne I.","family":"Lencer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Digestive Diseases Center, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1128\/MCB.06113-11","volume":"32","author":"Abe M","year":"2012","journal-title":"Mol Cell Biol"},{"key":"B2","doi-asserted-by":"crossref","first-page":"e16953","DOI":"10.1371\/journal.pone.0016953","volume":"6","author":"Angulo S","year":"2011","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"crossref","first-page":"C1453","DOI":"10.1152\/ajpcell.00189.2004","volume":"287","author":"Badizadegan K","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"B4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.1365-2958.1995.mmi_18040715.x","volume":"18","author":"Bajaj V","year":"1995","journal-title":"Mol Microbiol"},{"key":"B5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev.cb.07.110191.002005","volume":"7","author":"Bretscher A","year":"1991","journal-title":"Annu Rev Cell Biol"},{"key":"B6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0955-0674(99)80013-1","volume":"11","author":"Bretscher A","year":"1999","journal-title":"Curr Opin Cell Biol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/nrm882","volume":"3","author":"Bretscher A","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B8","doi-asserted-by":"crossref","first-page":"5325","DOI":"10.1242\/jcs.02635","volume":"118","author":"Chapman H","year":"2005","journal-title":"J Cell Sci"},{"key":"B9","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1471-4159.2001.00566.x","volume":"79","author":"Chik CL","year":"2001","journal-title":"J Neurochem"},{"key":"B10","doi-asserted-by":"crossref","first-page":"11247","DOI":"10.1021\/bi061307z","volume":"45","author":"Clarke CJ","year":"2006","journal-title":"Biochemistry"},{"key":"B11","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1242\/jcs.114.7.1331","volume":"114","author":"Criss AK","year":"2001","journal-title":"J Cell Sci"},{"key":"B12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-0854.2004.0170.x","volume":"5","author":"Devaux PF","year":"2004","journal-title":"Traffic"},{"key":"B13","doi-asserted-by":"crossref","first-page":"12895","DOI":"10.1073\/pnas.1402637111","volume":"111","author":"Eierhoff T","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/abbi.1997.9897","volume":"340","author":"Ella KM","year":"1997","journal-title":"Arch Biochem Biophys"},{"key":"B15","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1097\/00024382-200014060-00010","volume":"14","author":"Feltis BA","year":"2000","journal-title":"Shock"},{"key":"B16","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1242\/jcs.99.2.283","volume":"99","author":"Finlay BB","year":"1991","journal-title":"J Cell Sci"},{"key":"B17","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1042\/bst0120198","volume":"12","author":"Gilbert RJ","year":"1984","journal-title":"Biochem Soc Trans"},{"key":"B18","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1046\/j.1365-2958.1999.01486.x","volume":"33","author":"Gonzalez-Zorn B","year":"1999","journal-title":"Mol Microbiol"},{"key":"B19","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.cell.2012.05.008","volume":"149","author":"Gowrishankar K","year":"2015","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nm823","volume":"9","author":"Grassme H","year":"2003","journal-title":"Nat Med"},{"key":"B21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.imlet.2004.05.012","volume":"94","author":"Gri G","year":"2004","journal-title":"Immunol Lett"},{"key":"B22","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00109-004-0539-y","volume":"82","author":"Gulbins E","year":"2004","journal-title":"J Mol Med"},{"key":"B23","doi-asserted-by":"crossref","first-page":"7661","DOI":"10.1073\/pnas.94.14.7661","volume":"94","author":"Gulbins E","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"B24","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1016\/S0021-9258(17)41834-5","volume":"269","author":"Hannun YA","year":"1994","journal-title":"J Biol Chem"},{"key":"B25","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1172\/JCI113760","volume":"82","author":"Hecht G","year":"1988","journal-title":"J Clin Invest"},{"key":"B26","first-page":"117","volume":"282","author":"Hilpela P","year":"2004","journal-title":"Curr Top Microbiol Immunol"},{"key":"B27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.cell.2004.06.027","volume":"118","author":"Ho HY","year":"2004","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1365-2958.1995.mmi_18030479.x","volume":"18","author":"Hueck CJ","year":"1995","journal-title":"Mol Microbiol"},{"key":"B29","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.bbrc.2004.09.134","volume":"324","author":"Ito Y","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-02-0163"},{"key":"B31","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1172\/JCI117747","volume":"95","author":"Just I","year":"1995","journal-title":"J Clin Invest"},{"key":"B32","doi-asserted-by":"crossref","first-page":"24072","DOI":"10.1074\/jbc.M502244200","volume":"280","author":"Kiyokawa E","year":"2005","journal-title":"J Biol Chem"},{"key":"B33","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1128\/IAI.57.4.1290-1298.1989","volume":"57","author":"Knutton S","year":"1989","journal-title":"Infect Immun"},{"key":"B34","doi-asserted-by":"crossref","first-page":"10094","DOI":"10.1073\/pnas.92.22.10094","volume":"92","author":"Lencer WI","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"B35","doi-asserted-by":"crossref","first-page":"13795","DOI":"10.1073\/pnas.96.24.13795","volume":"96","author":"Lepple-Wienhues A","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"B36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1126\/science.1174621","volume":"327","author":"Lingwood D","year":"2010","journal-title":"Science"},{"key":"B37","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1006\/bbrc.1998.8329","volume":"245","author":"Liu Y","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"B38","first-page":"G416","volume":"254","author":"Madara JL","year":"1988","journal-title":"Am J Physiol"},{"key":"B39","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0016-5085(87)91069-9","volume":"92","author":"Madara JL","year":"1987","journal-title":"Gastroenterology"},{"key":"B40","doi-asserted-by":"crossref","first-page":"9997","DOI":"10.1074\/jbc.M309992200","volume":"279","author":"Megha","year":"2004","journal-title":"J Biol Chem"},{"key":"B41","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/taap.1996.8029","volume":"142","author":"Merrill AH","year":"1997","journal-title":"Toxicol Appl Pharmacol"},{"key":"B42","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1172\/JCI115741","volume":"89","author":"Nusrat A","year":"1992","journal-title":"J Clin Invest"},{"key":"B43","doi-asserted-by":"crossref","first-page":"10629","DOI":"10.1073\/pnas.92.23.10629","volume":"92","author":"Nusrat A","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"B44","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1083\/jcb.113.6.1267","volume":"113","author":"Pagano RE","year":"1991","journal-title":"J Cell Biol"},{"key":"B45","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1128\/IAI.55.12.3103-3110.1987","volume":"55","author":"Patel AH","year":"1987","journal-title":"Infect Immun"},{"key":"B46","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.1069784","volume":"292","author":"Pelkmans L","year":"2002","journal-title":"Science"},{"key":"B47","doi-asserted-by":"crossref","first-page":"22298","DOI":"10.1074\/jbc.273.35.22298","volume":"273","author":"Pike LJ","year":"1998","journal-title":"J Biol Chem"},{"key":"B48","first-page":"G1014","volume":"273","author":"Riegler M","year":"1997","journal-title":"Am J Physiol"},{"key":"B49","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2010.01.010","volume":"140","author":"Romer W","year":"2010","journal-title":"Cell"},{"key":"B50","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.devcel.2004.05.007","volume":"6","author":"Saotome I","year":"2004","journal-title":"Dev Cell"},{"key":"B51","first-page":"67","volume":"10","author":"Saslowsky DE","year":"2008","journal-title":"Cell Microbiol"},{"key":"B52","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1096\/fj.08-116467","volume":"23","author":"Saslowsky DE","year":"2009","journal-title":"FASEB J"},{"key":"B53","doi-asserted-by":"crossref","first-page":"25804","DOI":"10.1074\/jbc.M113.474957","volume":"288","author":"Saslowsky DE","year":"2013","journal-title":"J Biol Chem"},{"key":"B56","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3748\/wjg.v10.i12.1802","volume":"10","author":"Si JM","year":"2004","journal-title":"World J Gastroenterol"},{"key":"B54","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/42408","volume":"387","author":"Simons K","year":"1997","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.1021\/bi00417a001","volume":"27","author":"Simons K","year":"1988","journal-title":"Biochemistry"},{"key":"B57","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1016\/j.febslet.2008.08.016","volume":"582","author":"Sot J","year":"2008","journal-title":"FEBS Lett"},{"key":"B58","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1194\/jlr.M300103-JLR200","volume":"44","author":"Subbaiah PV","year":"2003","journal-title":"J Lipid Res"},{"key":"B59","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bbamem.2006.02.026","volume":"1758","author":"Taniguchi Y","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"B60","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1083\/jcb.109.4.1597","volume":"109","author":"Tilney LG","year":"1989","journal-title":"J Cell Biol"},{"key":"B61","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1128\/CMR.14.3.584-640.2001","volume":"14","author":"Vazquez-Boland JA","year":"2001","journal-title":"Clin Microbiol Rev"},{"key":"B62","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1083\/jcb.200107080","volume":"155","author":"Villalba M","year":"2001","journal-title":"J Cell Biol"},{"key":"B63","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1053\/gast.2001.27060","volume":"121","author":"Walsh SV","year":"2001","journal-title":"Gastroenterology"},{"key":"B64","doi-asserted-by":"crossref","first-page":"16249","DOI":"10.1074\/jbc.M109834200","volume":"277","author":"Wolf AA","year":"2002","journal-title":"J Biol Chem"},{"key":"B65","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1083\/jcb.200705060","volume":"181","author":"Zeidan YH","year":"2008","journal-title":"J Cell Biol"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T22:26:12Z","timestamp":1654295172000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E15-05-0293"}},"subtitle":[],"editor":[{"given":"Robert G.","family":"Parton","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":65,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1091\/mbc.E15-05-0293"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e15-05-0293","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}