Perilipin A and the control of triacylglycerol metabolism.
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.
Brasaemle
Dawn L
DL
Department of Nutritional Sciences, Rutgers, The State University of New Jersey, 96 Lipman Drive, New Brunswick, NJ 08901, USA. Brasaemle@aesop.rutgers.edu
Subramanian
Vidya
V
Garcia
Anne
A
Marcinkiewicz
Amy
A
Rothenberg
Alexis
A
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism*
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D014280:Triglycerides; D017868:Cyclic AMP-Dependent Protein Kinases