HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 17, 11901-11909, April 28, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/17/11901    most recent M600171200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marcinkiewicz, A. Articles by Brasaemle, D. L. Search for Related Content PubMed PubMed Citation Articles by Marcinkiewicz, A. Articles by Brasaemle, D. L. Social Bookmarking                      What's this?

The Phosphorylation of Serine 492 of Perilipin A Directs Lipid Droplet Fragmentation and Dispersion^*

From the Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901

Perilipin A is a key regulator of triacylglycerol storage and hydrolysis in adipocytes; phosphorylation of perilipin A by protein kinase A facilitates maximal lipolysis. Chronic stimulation of lipolysis in 3T3-L1 adipocytes causes large perinuclear lipid droplets to fragment into myriad dispersed perilipin A-covered microlipid droplets. In cultured fibroblasts stably expressing ectopic perilipin A, clustered lipid droplets disperse throughout the cytoplasm upon incubation of the cells with forskolin and isobutylmethylxanthine (IBMX) to elevate levels of cAMP and activate protein kinase A, mirroring events observed in adipocytes. Furthermore, diethylum-belliferyl phosphate inhibits stimulated lipolysis but not the dispersion of lipid droplets, suggesting that products of lipolysis are not required for this remodeling process. We hypothesized that protein kinase A-mediated phosphorylation of perilipin A triggers the remodeling of lipid droplets. The mutation of serine 492 of perilipin A to alanine prevented the dispersion of clustered lipid droplets in fibroblasts stably expressing the mutated perilipin upon incubation with forskolin and IBMX. In contrast, the substitution of serines 81, 222, 276, or 433 with alanine, either singly or in combinations, did not affect the protein kinase A-mediated remodeling of lipid droplets. Interestingly, substitution of serines 433, 492, and 517 of perilipin A with glutamic acid residues blocked the dispersion of clustered lipid droplets in cells incubated with forskolin and IBMX, indicating that the addition of a negative charge does not mimic a phosphate group. We conclude that protein kinase A-mediated phosphorylation of serine 492 of perilipin A drives the fragmentation and dispersion of lipid droplets.

Received for publication, January 6, 2006 , and in revised form, February 17, 2006.

^* This work was supported by National Institutes of Health Grant DK54797 and a Research Award from the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Nutritional Sciences, Rutgers, The State University of New Jersey, 96 Lipman Dr., New Brunswick, NJ 08901. Tel.: 732-932-6524; Fax: 732-932-6837; E-mail: Brasaemle{at}AESOP.Rutgers.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K.-A. Kim, S.-O Ka, W. S. Moon, H.-K. Yi, Y.-H. Lee, K.-B. Kwon, J.-W. Park, and B.-H. Park Effect of dermcidin, an antimicrobial peptide, on body fat mobilization in normal mice J. Endocrinol., July 1, 2008; 198(1): 111 - 118. [Abstract] [Full Text] [PDF]

				N. A. Ducharme and P. E. Bickel Minireview: Lipid Droplets in Lipogenesis and Lipolysis Endocrinology, March 1, 2008; 149(3): 942 - 949. [Abstract] [Full Text] [PDF]

				D. L. Brasaemle Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis J. Lipid Res., December 1, 2007; 48(12): 2547 - 2559. [Abstract] [Full Text] [PDF]

				C. Wang and R. J. St. Leger The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism, Appressorial Turgor Pressure, and Virulence J. Biol. Chem., July 20, 2007; 282(29): 21110 - 21115. [Abstract] [Full Text] [PDF]

				J. Laurencikiene, V. van Harmelen, E. Arvidsson Nordstrom, A. Dicker, L. Blomqvist, E. Naslund, D. Langin, P. Arner, and M. Ryden NF-{kappa}B is important for TNF-{alpha}-induced lipolysis in human adipocytes J. Lipid Res., May 1, 2007; 48(5): 1069 - 1077. [Abstract] [Full Text] [PDF]

				T. Yamaguchi, N. Omatsu, E. Morimoto, H. Nakashima, K. Ueno, T. Tanaka, K. Satouchi, F. Hirose, and T. Osumi CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation J. Lipid Res., May 1, 2007; 48(5): 1078 - 1089. [Abstract] [Full Text] [PDF]

				J. Buchmann, C. Meyer, S. Neschen, R. Augustin, K. Schmolz, R. Kluge, H. Al-Hasani, H. Jurgens, K. Eulenberg, R. Wehr, et al. Ablation of the Cholesterol Transporter Adenosine Triphosphate-Binding Cassette Transporter G1 Reduces Adipose Cell Size and Protects against Diet-Induced Obesity Endocrinology, April 1, 2007; 148(4): 1561 - 1573. [Abstract] [Full Text] [PDF]

				H. Miyoshi, J. W. Perfield II, S. C. Souza, W.-J. Shen, H.-H. Zhang, Z. S. Stancheva, F. B. Kraemer, M. S. Obin, and A. S. Greenberg Control of Adipose Triglyceride Lipase Action by Serine 517 of Perilipin A Globally Regulates Protein Kinase A-stimulated Lipolysis in Adipocytes J. Biol. Chem., January 12, 2007; 282(2): 996 - 1002. [Abstract] [Full Text] [PDF]

				E. L. Arrese, R. T. Patel, and J. L. Soulages The main triglyceride-lipase from the insect fat body is an active phospholipase A1: identification and characterization J. Lipid Res., December 1, 2006; 47(12): 2656 - 2667. [Abstract] [Full Text] [PDF]

				H. Miyoshi, S. C. Souza, H.-H. Zhang, K. J. Strissel, M. A. Christoffolete, J. Kovsan, A. Rudich, F. B. Kraemer, A. C. Bianco, M. S. Obin, et al. Perilipin Promotes Hormone-sensitive Lipase-mediated Adipocyte Lipolysis via Phosphorylation-dependent and -independent Mechanisms J. Biol. Chem., June 9, 2006; 281(23): 15837 - 15844. [Abstract] [Full Text] [PDF]