title: All members in the sphingomyelin synthase gene family have ceramide phosphoethanolamine synthase activity.
abstract: Sphingomyelin synthase-related protein (SMSr) synthesizes the sphingomyelin analog ceramide phosphoethanolamine (CPE) in cells. Previous cell studies indicated that SMSr is involved in ceramide homeostasis and is crucial for cell function. To further examine SMSr function in vivo, we generated Smsr KO mice that were fertile and had no obvious phenotypic alterations. Quantitative MS analyses of plasma, liver, and macrophages from the KO mice revealed only marginal changes in CPE and ceramide as well as other sphingolipid levels. Because SMS2 also has CPE synthase activity, we prepared Smsr/Sms2 double KO mice. We found that CPE levels were not significantly changed in macrophages, suggesting that CPE levels are not exclusively dependent on SMSr and SMS2 activities. We then measured CPE levels in Sms1 KO mice and found that Sms1 deficiency also reduced plasma CPE levels. Importantly, we found that expression of Sms1 or Sms2 in SF9 insect cells significantly increased not only SM but also CPE formation, indicating that SMS1 also has CPE synthase activity. Moreover, we measured CPE synthase Km and Vmax for SMS1, SMS2, and SMSr using different NBD ceramides. Our study reveals that all mouse SMS family members (SMSr, SMS1, and SMS2) have CPE synthase activity. However, neither CPE nor SMSr appears to be a critical regulator of ceramide levels in vivo.
authors.affiliation: School of Pharmacy, Fudan University, China; Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Ding
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Inamul
authors.initials: I
authors.lastname: Kabir
authors.affiliation: School of Pharmacy, Fudan University, China; Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY; Guangdong Medical Laboratory Animal Center, Foshan, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Lou
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Amirfarbod
authors.initials: A
authors.lastname: Yazdanyar
authors.affiliation: School of Pharmacy, Fudan University, China.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Fudan University, China.
authors.forename: Jibin
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Life Science, Gachon University, Sungnam, 461-701, South Korea.
authors.forename: Taesik
authors.initials: T
authors.lastname: Park
authors.affiliation: Guangdong Medical Laboratory Animal Center, Foshan, China.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boutjdir
authors.affiliation: Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmacy, Fudan University, China; Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY; Molecular and Cellular Cardiology Program, VA New York Harbor Healthcare System, Brooklyn, NY. Electronic address: xjiang@downstate.edu.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
mesh_terms: D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D013109:Sphingomyelins / Q000096:biosynthesis* / Q000235:genetics; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism*
chemical_list: D013109:Sphingomyelins; C060281:ceramide phosphoethanolamine; C556686:Sgms1 protein, mouse; D017855:Transferases (Other Substituted Phosphate Groups); C543123:Sgms2 protein, mouse
keywords: mouse gene knockout; sphingomyelin synthase 1; sphingomyelin synthase 2; sphingomyelin synthase-related protein