Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control
Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess the...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520437204 |
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| author | Stacey N. Keenan William De Nardo Jieqiong Lou Ralf B. Schittenhelm Magdalene K. Montgomery James G. Granneman Elizabeth Hinde Matthew J. Watt |
| author_facet | Stacey N. Keenan William De Nardo Jieqiong Lou Ralf B. Schittenhelm Magdalene K. Montgomery James G. Granneman Elizabeth Hinde Matthew J. Watt |
| author_sort | Stacey N. Keenan |
| collection | DOAJ |
| description | Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155 and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis compared with wild-type PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism. |
| first_indexed | 2024-12-20T16:56:46Z |
| format | Article |
| id | doaj.art-fa5a9be0f3824de49839e18d04e01713 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T16:56:46Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fa5a9be0f3824de49839e18d04e017132022-12-21T19:32:42ZengElsevierJournal of Lipid Research0022-22752021-01-0162100016Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic controlStacey N. Keenan0William De Nardo1Jieqiong Lou2Ralf B. Schittenhelm3Magdalene K. Montgomery4James G. Granneman5Elizabeth Hinde6Matthew J. Watt7Department of Physiology, University of Melbourne, Melbourne, Victoria, AustraliaDepartment of Physiology, University of Melbourne, Melbourne, Victoria, AustraliaSchool of Physics, University of Melbourne, Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Melbourne, Victoria, AustraliaMonash Proteomics & Metabolomics Facility and Department of Biochemistry and Molecular Biology, Monash University, Victoria, AustraliaDepartment of Physiology, University of Melbourne, Melbourne, Victoria, AustraliaCenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USASchool of Physics, University of Melbourne, Melbourne, Victoria, Australia; Department of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Melbourne, Victoria, AustraliaDepartment of Physiology, University of Melbourne, Melbourne, Victoria, Australia; For correspondence: Matthew J. WattPerilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155 and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis compared with wild-type PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism.http://www.sciencedirect.com/science/article/pii/S0022227520437204lipid dropletsperilipinslipasetriglyceridefatty acidprotein kinase A |
| spellingShingle | Stacey N. Keenan William De Nardo Jieqiong Lou Ralf B. Schittenhelm Magdalene K. Montgomery James G. Granneman Elizabeth Hinde Matthew J. Watt Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control Journal of Lipid Research lipid droplets perilipins lipase triglyceride fatty acid protein kinase A |
| title | Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control |
| title_full | Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control |
| title_fullStr | Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control |
| title_full_unstemmed | Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control |
| title_short | Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control |
| title_sort | perilipin 5 s155 phosphorylation by pka is required for the control of hepatic lipid metabolism and glycemic control |
| topic | lipid droplets perilipins lipase triglyceride fatty acid protein kinase A |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520437204 |
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