{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:05:38Z","timestamp":1776877538302,"version":"3.51.2"},"reference-count":44,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2012,12,19]],"date-time":"2012-12-19T00:00:00Z","timestamp":1355875200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Electrophoresis"],"published-print":{"date-parts":[[2012,12]]},"abstract":"Four patients with juvenile neuronal ceroid lipofuscinoses, a childhood neurodegenerative disorder that was previously described as CLN<\/jats:styled-content>9 variant, are reclassified as CLN<\/jats:styled-content>5 disease. CLN<\/jats:styled-content>5\u2010deficient (CLN<\/jats:italic><\/jats:styled-content>5\u2212\/\u2212<\/jats:sup><\/jats:italic>) fibroblasts demonstrate adhesion defects, increased growth, apoptosis, and decreased levels of ceramide, sphingomyelin, and glycosphingolipids. The CLN<\/jats:styled-content>8 protein (CLN<\/jats:styled-content>8p) corrects growth and apoptosis in CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic>\u2212\/\u2212<\/jats:sup> cells. Related proteins containing a L<\/jats:styled-content>ag1 motif (C<\/jats:styled-content>erS<\/jats:styled-content>1\/2\/4\/5\/6) partially corrected these deficits, with C<\/jats:styled-content>erS<\/jats:styled-content>1, which is primarily expressed in brain, providing the best complementation, suggesting CLN<\/jats:styled-content>5p activates C<\/jats:styled-content>erS<\/jats:styled-content>1 and may co\u2010immunoprecipitate with it. CLN<\/jats:styled-content>8p complements CLN<\/jats:styled-content>5\u2010deficient cells, consolidating the interrelationship of CLN<\/jats:styled-content>5p\/CLN<\/jats:styled-content>8p, whose potential roles are explored as activators of (dihydro)ceramide synthases. Homozygosity mapping using microarray technology led to identification of CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic> as the culprit gene in previously classified CLN<\/jats:styled-content>9\u2010defective cases. Similar to CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic>\u2212\/\u2212<\/jats:sup>cells, ceramide synthase activity, C<\/jats:styled-content>16\/C<\/jats:styled-content>18:0\/C<\/jats:styled-content>24:0\/C<\/jats:styled-content>24:1 ceramide species, measured by MS is decreased in CLN<\/jats:italic><\/jats:styled-content>8\u2212\/\u2212<\/jats:sup><\/jats:italic> cells. Comparison of normal versus CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic>\u2212\/\u2212<\/jats:sup> cell C<\/jats:styled-content>erS<\/jats:styled-content>1\u2010bound proteins by immunoprecipitation, differential gel electrophoresis, and MS revealed absence of \u03b3\u2010actin in CLN<\/jats:italic><\/jats:styled-content>5\u2212\/\u2212<\/jats:sup><\/jats:italic> cells. The \u03b3\u2010actin gene sequence is normal in CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic>\u2212\/\u2212<\/jats:sup> derived DNA<\/jats:styled-content>. The \u03b3\u2010actin\u2010bound proteins, vimentin and histones H<\/jats:styled-content>2A<\/jats:styled-content>fz\/H<\/jats:styled-content>3F<\/jats:styled-content>3A<\/jats:styled-content>\/H<\/jats:styled-content>ist1H<\/jats:styled-content>4, were absent from the \u03b3\u2010actin protein complex in CLN<\/jats:italic><\/jats:styled-content>5<\/jats:italic>\u2212\/\u2212<\/jats:sup> cells. The function of CLN<\/jats:styled-content>5p may require vimentin and the histone proteins to bind \u03b3\u2010actin. Defective binding could explain the CLN<\/jats:styled-content>5\u2212\/\u2212<\/jats:sup> cellular phenotype. We explore the role of the CLN<\/jats:styled-content>5\/CLN<\/jats:styled-content>8 proteins in ceramide species specific sphingolipid de novo synthesis, and suggest that CLN<\/jats:styled-content>5\/CLN<\/jats:styled-content>8 proteins are more closely related than previously believed.<\/jats:p>","DOI":"10.1002\/elps.201200472","type":"journal-article","created":{"date-parts":[[2012,10,18]],"date-time":"2012-10-18T11:54:15Z","timestamp":1350561255000},"page":"3798-3809","source":"Crossref","is-referenced-by-count":54,"title":["CLN<\/scp>5 and CLN<\/scp>8 protein association with ceramide synthase: B<\/scp>iochemical and proteomic approaches"],"prefix":"10.1002","volume":"33","author":[{"given":"Saria El","family":"Haddad","sequence":"first","affiliation":[{"name":"Neurogenetics Program and Division of Pediatric Neurology Departments of Pediatric and Adolescent Medicine Biochemistry and Molecular Genetics American University of Beirut Beirut 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