Abstract
Perilipin A is the most abundant protein associated with the lipid droplets of adipocytes and functions to control both basal and stimulated lipolysis. Under basal or fed conditions, perilipin A shields stored triacylglycerols from cytosolic lipases, thus promoting triacylglycerol storage. When catecholamines bind to cell surface receptors to initiate signals that activate cAMP-dependent protein kinase (PKA), phosphorylated perilipin A facilitates maximal lipolysis. Mutagenesis studies have revealed that central sequences of moderately hydrophobic amino acids are required to target nascent perilipin A to lipid droplets and provide an anchor into the hydrophobic environment of lipid droplets. Sequences of amino acids in the unique carboxyl terminus of perilipin A and those in amino terminal sequences flanking the first hydrophobic stretch are required for the barrier function of perilipin A in promoting triacylglycerol storage. Site-directed mutagenesis studies of serine residues within six PKA consensus sites of perilipin A reveal functions for phosphorylation of at least three of the sites. Phosphorylation of one or more of the serines within three amino terminal PKA sites is required to facilitate hormone-sensitive lipase access to lipid substrates. Phosphorylation of serines within two carboxyl terminal sites is also required for maximal lipolysis. Phosphorylation of serine 492 (site 5) triggers a massive remodeling of lipid droplets, whereby large peri-nuclear lipid droplets fragment into myriad lipid micro-droplets that scatter throughout the cytoplasm. We hypothesize that perilipin A binds accessory proteins to provide assistance in carrying out these functions.
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Abbreviations
- ATGL:
-
Adipose triglyceride lipase
- HSL:
-
Hormone-sensitive lipase
- IBMX:
-
Isobutylmethylxanthine
- PKA:
-
Protein kinase A (cAMP-dependent protein kinase)
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Acknowledgments
Research has been supported by NIH R01 DK54797, an Established Investigator Award from the American Heart Association, a Research Award from the American Diabetes Association, and Johnson & Johnson Discovery Awards administered through Rutgers University.
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Brasaemle, D.L., Subramanian, V., Garcia, A. et al. Perilipin A and the control of triacylglycerol metabolism. Mol Cell Biochem 326, 15–21 (2009). https://doi.org/10.1007/s11010-008-9998-8
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DOI: https://doi.org/10.1007/s11010-008-9998-8