The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2
During the last 30 years, an increasing number of cellular functions have been reported to be regulated by the lipid ceramide. The diversity in the ceramide structure, leading to tens of ceramide species and the discrete distribution based on subcellular topology, could explain the wide variety of f...
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Elsevier
2025-01-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227524002244 |
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| author | Anne G. Ostermeyer-Fay Abhay Kanodia Ranjana Pathak Maria Jose Hernandez-Corbacho Aarnoud C. van der Spoel Yusuf A. Hannun Daniel Canals |
| author_facet | Anne G. Ostermeyer-Fay Abhay Kanodia Ranjana Pathak Maria Jose Hernandez-Corbacho Aarnoud C. van der Spoel Yusuf A. Hannun Daniel Canals |
| author_sort | Anne G. Ostermeyer-Fay |
| collection | DOAJ |
| description | During the last 30 years, an increasing number of cellular functions have been reported to be regulated by the lipid ceramide. The diversity in the ceramide structure, leading to tens of ceramide species and the discrete distribution based on subcellular topology, could explain the wide variety of functions attributed to this bioactive lipid. One of these pools of ceramide resides in the plasma membrane, and several works have suggested that an increase in plasma membrane ceramide (PMCer) in response to stimulation leads to cell death and modulates cell adhesion and migration. However, there is a limitation in studying PMCer content in this location primarily due to the inability to quantify its mass. Our group recently developed a method to specifically quantitate PMCer. In this work, we interrogate what sphingolipid metabolizing enzymes are responsible for modulating the basal levels of plasma membrane ceramide. An in-silico prediction and experimental confirmation found an almost perfect correlation between the endogenous expression levels of neutral sphingomyelinase (nSMase2) and the amount of plasma membrane ceramide in unstimulated cells. Manipulating the expression levels of nSMase2, but not other candidate enzymes of ceramide metabolism, profoundly affected PMCer. Moreover, a physiologic induction of nSMase2 during cell confluence resulted in a nSMase2-dependent dramatic increase in PMCer. Together, these results identify nSMase2 as the primary enzyme to regulate plasma membrane ceramide. |
| format | Article |
| id | doaj-art-82327d7cabfe4d3eacc4f14ab3ff4469 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-82327d7cabfe4d3eacc4f14ab3ff44692025-01-30T05:12:39ZengElsevierJournal of Lipid Research0022-22752025-01-01661100719The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2Anne G. Ostermeyer-Fay0Abhay Kanodia1Ranjana Pathak2Maria Jose Hernandez-Corbacho3Aarnoud C. van der Spoel4Yusuf A. Hannun5Daniel Canals6Department of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USADepartment of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY, USADepartment of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USADepartment of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USAThe Atlantic Research Centre, Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia, CanadaDepartment of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USA; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA; Department of Pathology, Stony Brook University, Stony Brook, NY, USADepartment of Medicine, Cancer Center at Stony Brook, Stony Brook, NY, USA; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA; Biological Mass Spectrometry Center, Stony Brook University, Stony Brook, NY, USA; For correspondence: Daniel CanalsDuring the last 30 years, an increasing number of cellular functions have been reported to be regulated by the lipid ceramide. The diversity in the ceramide structure, leading to tens of ceramide species and the discrete distribution based on subcellular topology, could explain the wide variety of functions attributed to this bioactive lipid. One of these pools of ceramide resides in the plasma membrane, and several works have suggested that an increase in plasma membrane ceramide (PMCer) in response to stimulation leads to cell death and modulates cell adhesion and migration. However, there is a limitation in studying PMCer content in this location primarily due to the inability to quantify its mass. Our group recently developed a method to specifically quantitate PMCer. In this work, we interrogate what sphingolipid metabolizing enzymes are responsible for modulating the basal levels of plasma membrane ceramide. An in-silico prediction and experimental confirmation found an almost perfect correlation between the endogenous expression levels of neutral sphingomyelinase (nSMase2) and the amount of plasma membrane ceramide in unstimulated cells. Manipulating the expression levels of nSMase2, but not other candidate enzymes of ceramide metabolism, profoundly affected PMCer. Moreover, a physiologic induction of nSMase2 during cell confluence resulted in a nSMase2-dependent dramatic increase in PMCer. Together, these results identify nSMase2 as the primary enzyme to regulate plasma membrane ceramide.http://www.sciencedirect.com/science/article/pii/S0022227524002244neutral sphingomyelinase 2acid sphingomyelinaseGBA2sphingomyelin synthase 2neutral ceramidaseacid ceramidase |
| spellingShingle | Anne G. Ostermeyer-Fay Abhay Kanodia Ranjana Pathak Maria Jose Hernandez-Corbacho Aarnoud C. van der Spoel Yusuf A. Hannun Daniel Canals The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 Journal of Lipid Research neutral sphingomyelinase 2 acid sphingomyelinase GBA2 sphingomyelin synthase 2 neutral ceramidase acid ceramidase |
| title | The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| title_full | The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| title_fullStr | The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| title_full_unstemmed | The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| title_short | The steady-state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| title_sort | steady state level of plasma membrane ceramide is regulated by neutral sphingomyelinase 2 |
| topic | neutral sphingomyelinase 2 acid sphingomyelinase GBA2 sphingomyelin synthase 2 neutral ceramidase acid ceramidase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227524002244 |
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