Perilipin A and the control of triacylglycerol metabolism

被引:144
作者
Brasaemle, Dawn L. [1 ]
Subramanian, Vidya [1 ]
Garcia, Anne [1 ]
Marcinkiewicz, Amy [1 ]
Rothenberg, Alexis [1 ]
机构
[1] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08901 USA
关键词
Adipocyte; Lipid droplet; Lipolysis; Protein kinase A; Hormone-sensitive lipase; HORMONE-SENSITIVE LIPASE; ADIPOSE TRIGLYCERIDE LIPASE; DIFFERENTIATION-RELATED PROTEIN; DROPLET-ASSOCIATED PROTEINS; A-MEDIATED LIPOLYSIS; LIPID DROPLETS; STIMULATED LIPOLYSIS; POSTTRANSLATIONAL REGULATION; ADIPOCYTE LIPOLYSIS; FAT STORAGE;
D O I
10.1007/s11010-008-9998-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:15 / 21
页数:7
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