JBC Advanced Glycation Endproducts

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M600171200 on February 17, 2006

J. Biol. Chem., Vol. 281, Issue 17, 11901-11909, April 28, 2006
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
281/17/11901    most recent
M600171200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Marcinkiewicz, A.
Right arrow Articles by Brasaemle, D. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marcinkiewicz, A.
Right arrow Articles by Brasaemle, D. L.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

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

Amy Marcinkiewicz, Denise Gauthier, Anne Garcia, and Dawn L. Brasaemle1

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.


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


This article has been cited by other articles:


Home page
J EndocrinolHome page
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]


Home page
EndocrinologyHome page
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]


Home page
J. Lipid Res.Home page
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]


Home page
J. Biol. Chem.Home page
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]


Home page
J. Lipid Res.Home page
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]


Home page
J. Lipid Res.Home page
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]


Home page
EndocrinologyHome page
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]


Home page
J. Biol. Chem.Home page
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]


Home page
J. Lipid Res.Home page
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]


Home page
J. Biol. Chem.Home page
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]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.