Perilipin A and the control of triacylglycerol metabolism

  • Dawn L. Brasaemle
  • Vidya Subramanian
  • Anne Garcia
  • Amy Marcinkiewicz
  • Alexis Rothenberg
Article

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.

Keywords

Adipocyte Lipid droplet Lipolysis Protein kinase A Hormone-sensitive lipase 

Abbreviations

ATGL

Adipose triglyceride lipase

HSL

Hormone-sensitive lipase

IBMX

Isobutylmethylxanthine

PKA

Protein kinase A (cAMP-dependent protein kinase)

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Dawn L. Brasaemle
    • 1
  • Vidya Subramanian
    • 1
  • Anne Garcia
    • 1
  • Amy Marcinkiewicz
    • 1
  • Alexis Rothenberg
    • 1
  1. 1.Department of Nutritional Sciences, RutgersThe State University of New JerseyNew BrunswickUSA

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