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ASM-deficient cells, including human cells from Niemann-Pick type A (NPA) patients, undergo lysosomal exocytosis after wounding but are defective in injury-dependent endocytosis and plasma membrane repair. Exogenously added recombinant human ASM restores endocytosis and resealing in ASM-depleted cells, suggesting that conversion of plasma membrane sphingomyelin to ceramide by this lysosomal enzyme promotes lesion internalization. These findings reveal a molecular mechanism for restoration of plasma membrane integrity through exocytosis of lysosomes and identify defective plasma membrane repair as a possible component of the severe pathology observed in NPA patients.<\/jats:p>","DOI":"10.1083\/jcb.201003053","type":"journal-article","created":{"date-parts":[[2010,6,8]],"date-time":"2010-06-08T04:15:54Z","timestamp":1275970554000},"page":"1027-1038","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":353,"title":["Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair"],"prefix":"10.1083","volume":"189","author":[{"given":"Christina","family":"Tam","sequence":"first","affiliation":[{"name":"Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536 1"},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Idone","sequence":"additional","affiliation":[{"name":"Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Devlin","sequence":"additional","affiliation":[{"name":"Indiana University\u2013Purdue University School of Medicine, Indianapolis, IN 46202 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cecilia","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Flannery","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Schuchman","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Tabas","sequence":"additional","affiliation":[{"name":"Department of Medicine 5 , 6 , and 7"},{"name":"Department of Pathology and Cell Biology 5 , 6 , and 7"},{"name":"Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10027 5 , 6 , and 7"},{"name":"Department of Medicine 5 , 6 , and 7"},{"name":"Department of Pathology and Cell Biology 5 , 6 , and 7"},{"name":"Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10027 5 , 6 , and 7"},{"name":"Department of Medicine 5 , 6 , and 7"},{"name":"Department of Pathology and Cell Biology 5 , 6 , and 7"},{"name":"Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10027 5 , 6 , and 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma W.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536 1"},{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,6,7]]},"reference":[{"key":"2023072223522570400_bib1","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1083\/jcb.101.6.2210","article-title":"Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border","volume":"101","author":"Baron","year":"1985","journal-title":"J. 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