|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 10, 8401-8406, March 7, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Laboratory of Cellular and Developmental Biology,
NIDDK, National Institutes of Health,
Bethesda, Maryland 20892-8028
Perilipin A coats the lipid storage droplets in
adipocytes and is polyphosphorylated by protein kinase A (PKA); the
fact that PKA activates lipolysis in adipocytes suggests a role for
perilipins in this process. To assess whether perilipins participate
directly in PKA-mediated lipolysis, we have expressed constructs coding for native and mutated forms of the two major splice variants of the
perilipin gene, perilipins A and B, in Chinese hamster ovary
fibroblasts. Perilipins localize to lipid droplet surfaces and displace
the adipose differentiation-related protein that normally coats the
droplets in these cells. Perilipin A inhibits triacylglycerol
hydrolysis by 87% when PKA is quiescent, but activation of PKA and
phosphorylation of perilipin A engenders a 7-fold lipolytic activation.
Mutation of PKA sites within the N-terminal region of perilipin
abrogates the PKA-mediated lipolytic response. In contrast, perilipin B
exerts only minimal protection against lipolysis and is unresponsive to
PKA activation. Since Chinese hamster ovary cells contain no
PKA-activated lipase, we conclude that the expression of perilipin A
alone is sufficient to confer PKA-mediated lipolysis in these cells.
Moreover, the data indicate that the unique C-terminal portion of
perilipin A is responsible for its protection against lipolysis and
that phosphorylation at the N-terminal PKA sites attenuates this
protective effect.
Functional Studies on Native and Mutated Forms of
Perilipins
A ROLE IN PROTEIN KINASE A-MEDIATED LIPOLYSIS OF
TRIACYLGLYCEROLS IN CHINESE HAMSTER OVARY CELLS*
,
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Dept. of Chemistry, Otterbein College,
Westerville, OH 43081-2006.
§
Present address: Dept. of Nutritional Sciences, Rutgers, The State
University of New Jersey, New Brunswick, NJ 08901.
¶
To whom correspondence should be addressed: Bldg. 50, Rm.
3140, National Institutes of Health, Bethesda, MD 20892-8028. Tel.: 301-496-6991; Fax: 301-496-5239; E-mail:
DeanL@intra.niddk.nih.gov.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Borg, C. Klint, N. Wierup, K. Strom, S. Larsson, F. Sundler, R. Lupi, P. Marchetti, G. Xu, A. Kimmel, et al. Perilipin Is Present in Islets of Langerhans and Protects against Lipotoxicity When Overexpressed in the {beta}-Cell Line INS-1 Endocrinology, July 1, 2009; 150(7): 3049 - 3057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Bulankina, A. Deggerich, D. Wenzel, K. Mutenda, J. G. Wittmann, M. G. Rudolph, K. N.J. Burger, and S. Honing TIP47 functions in the biogenesis of lipid droplets J. Cell Biol., May 18, 2009; 185(4): 641 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zechner, P. C. Kienesberger, G. Haemmerle, R. Zimmermann, and A. Lass Adipose triglyceride lipase and the lipolytic catabolism of cellular fat stores J. Lipid Res., January 1, 2009; 50(1): 3 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Anderson and J. Borlak Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bell, H. Wang, H. Chen, J. C. McLenithan, D.-W. Gong, R.-Z. Yang, D. Yu, S. K. Fried, M. J. Quon, C. Londos, et al. Consequences of Lipid Droplet Coat Protein Downregulation in Liver Cells: Abnormal Lipid Droplet Metabolism and Induction of Insulin Resistance Diabetes, August 1, 2008; 57(8): 2037 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Keller, J. T. Petrie, P. De Rose, I. Gerin, W. S. Wright, S.-H. Chiang, A. R. Nielsen, C. P. Fischer, B. K. Pedersen, and O. A. MacDougald Fat-specific Protein 27 Regulates Storage of Triacylglycerol J. Biol. Chem., May 23, 2008; 283(21): 14355 - 14365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Perez-Martinez, N. Yiannakouris, J. Lopez-Miranda, D. Arnett, M. Tsai, E. Galan, R. Straka, J. Delgado-Lista, M. Province, J. Ruano, et al. Postprandial triacylglycerol metabolism is modified by the presence of genetic variation at the perilipin (PLIN) locus in 2 white populations Am. J. Clinical Nutrition, March 1, 2008; 87(3): 744 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C Harmer, D. J Pepper, K. Cooke, H. P J Bennett, and A. B Bicknell Evidence of a possible role for Lys-{gamma}3-MSH in the regulation of adipocyte function J. Endocrinol., January 1, 2008; 196(1): 149 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Listenberger, A. G. Ostermeyer-Fay, E. B. Goldberg, W. J. Brown, and D. A. Brown Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover J. Lipid Res., December 1, 2007; 48(12): 2751 - 2761. [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]
|
|
|
|
|
|
D. M. Schwartz and N. E. Wolins A simple and rapid method to assay triacylglycerol in cells and tissues J. Lipid Res., November 1, 2007; 48(11): 2514 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Souza, M. A. Christoffolete, M. O. Ribeiro, H. Miyoshi, K. J. Strissel, Z. S. Stancheva, N. H. Rogers, T. M. D'Eon, J. W. Perfield II, H. Imachi, et al. Perilipin regulates the thermogenic actions of norepinephrine in brown adipose tissue J. Lipid Res., June 1, 2007; 48(6): 1273 - 1279. [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]
|
|
|
|
|
|
M. Schweiger, R. Schreiber, G. Haemmerle, A. Lass, C. Fledelius, P. Jacobsen, H. Tornqvist, R. Zechner, and R. Zimmermann Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism J. Biol. Chem., December 29, 2006; 281(52): 40236 - 40241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sztalryd, M. Bell, X. Lu, P. Mertz, S. Hickenbottom, B. H.-J. Chang, L. Chan, A. R. Kimmel, and C. Londos Functional Compensation for Adipose Differentiation-related Protein (ADFP) by Tip47 in an ADFP Null Embryonic Cell Line J. Biol. Chem., November 10, 2006; 281(45): 34341 - 34348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Prats, M. Donsmark, K. Qvortrup, C. Londos, C. Sztalryd, C. Holm, H. Galbo, and T. Ploug Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine J. Lipid Res., November 1, 2006; 47(11): 2392 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kang and L. E. Nagy Chronic Ethanol Feeding Suppresses {beta}-Adrenergic Receptor-Stimulated Lipolysis in Adipocytes Isolated from Epididymal Fat Endocrinology, September 1, 2006; 147(9): 4330 - 4338. [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]
|
|
|
|
 |
|
 E. S. Kang, B. S. Cha, H. J. Kim, H. J. Kim, S. H. Kim, K. Y. Hur, H. J. Lee, W. S. Shim, C. W. Ahn, and H. C. Lee The 11482G>A Polymorphism in the Perilipin Gene Is Associated With Weight Gain With Rosiglitazone Treatment in Type 2 Diabetes. Diabetes Care, June 1, 2006; 29(6): 1320 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Beller, D. Riedel, L. Jansch, G. Dieterich, J. Wehland, H. Jackle, and R. P. Kuhnlein Characterization of the Drosophila Lipid Droplet Subproteome Mol. Cell. Proteomics, June 1, 2006; 5(6): 1082 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Marcinkiewicz, D. Gauthier, A. Garcia, and D. L. Brasaemle The Phosphorylation of Serine 492 of Perilipin A Directs Lipid Droplet Fragmentation and Dispersion J. Biol. Chem., April 28, 2006; 281(17): 11901 - 11909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H.-J. Chang, L. Li, A. Paul, S. Taniguchi, V. Nannegari, W. C. Heird, and L. Chan Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein Mol. Cell. Biol., February 1, 2006; 26(3): 1063 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Gross, H. Miyoshi, T. Hosaka, H.-H. Zhang, E. C. Pino, S. Souza, M. Obin, A. S. Greenberg, and P. F. Pilch Dynamics of Lipid Droplet-Associated Proteins during Hormonally Stimulated Lipolysis in Engineered Adipocytes: Stabilization and Lipid Droplet Binding of Adipocyte Differentiation-Related Protein/Adipophilin Mol. Endocrinol., February 1, 2006; 20(2): 459 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xu, C. Sztalryd, X. Lu, J. T. Tansey, J. Gan, H. Dorward, A. R. Kimmel, and C. Londos Post-translational Regulation of Adipose Differentiation-related Protein by the Ubiquitin/Proteasome Pathway J. Biol. Chem., December 30, 2005; 280(52): 42841 - 42847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Forcheron, L. Legedz, G. Chinetti, P. Feugier, D. Letexier, G. Bricca, and M. Beylot Genes of Cholesterol Metabolism in Human Atheroma: Overexpression of Perilipin and Genes Promoting Cholesterol Storage and Repression of ABCA1 Expression Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1711 - 1717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Patel, J. L. Soulages, B. Hariharasundaram, and E. L. Arrese Activation of the Lipid Droplet Controls the Rate of Lipolysis of Triglycerides in the Insect Fat Body J. Biol. Chem., June 17, 2005; 280(24): 22624 - 22631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Adler-Wailes, H. Liu, F. Ahmad, N. Feng, C. Londos, V. Manganiello, and J. A. Yanovski Effects of the Human Immunodeficiency Virus-Protease Inhibitor, Ritonavir, on Basal and Catecholamine-Stimulated Lipolysis J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3251 - 3261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Schadinger, N. L. R. Bucher, B. M. Schreiber, and S. R. Farmer PPAR{gamma}2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes Am J Physiol Endocrinol Metab, June 1, 2005; 288(6): E1195 - E1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Snyder, J. M. Esselstyn, K. Loughney, S. L. Wolda, and V. A. Florio The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis J. Lipid Res., March 1, 2005; 46(3): 494 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Smith, M. A. Sanders, B. R. Thompson, C. Londos, F. B. Kraemer, and D. A. Bernlohr Physical Association between the Adipocyte Fatty Acid-binding Protein and Hormone-sensitive Lipase: A FLUORESCENCE RESONANCE ENERGY TRANSFER ANALYSIS J. Biol. Chem., December 10, 2004; 279(50): 52399 - 52405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Brasaemle, G. Dolios, L. Shapiro, and R. Wang Proteomic Analysis of Proteins Associated with Lipid Droplets of Basal and Lipolytically Stimulated 3T3-L1 Adipocytes J. Biol. Chem., November 5, 2004; 279(45): 46835 - 46842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Subramanian, A. Garcia, A. Sekowski, and D. L. Brasaemle Hydrophobic sequences target and anchor perilipin A to lipid droplets J. Lipid Res., November 1, 2004; 45(11): 1983 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Subramanian, A. Rothenberg, C. Gomez, A. W. Cohen, A. Garcia, S. Bhattacharyya, L. Shapiro, G. Dolios, R. Wang, M. P. Lisanti, et al. Perilipin A Mediates the Reversible Binding of CGI-58 to Lipid Droplets in 3T3-L1 Adipocytes J. Biol. Chem., October 1, 2004; 279(40): 42062 - 42071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cohen, B. Razani, W. Schubert, T. M. Williams, X. B. Wang, P. Iyengar, D. L. Brasaemle, P. E. Scherer, and M. P. Lisanti Role of Caveolin-1 in the Modulation of Lipolysis and Lipid Droplet Formation Diabetes, May 1, 2004; 53(5): 1261 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nagai, C. Shimizu, M. Umetsu, S. Taniguchi, M. Endo, H. Miyoshi, N. Yoshioka, M. Kubo, and T. Koike Identification of a Functional Peroxisome Proliferator-Activated Receptor Responsive Element within the Murine Perilipin Gene Endocrinology, May 1, 2004; 145(5): 2346 - 2356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Arimura, T. Horiba, M. Imagawa, M. Shimizu, and R. Sato The Peroxisome Proliferator-activated Receptor {gamma} Regulates Expression of the Perilipin Gene in Adipocytes J. Biol. Chem., March 12, 2004; 279(11): 10070 - 10076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garcia, V. Subramanian, A. Sekowski, S. Bhattacharyya, M. W. Love, and D. L. Brasaemle The Amino and Carboxyl Termini of Perilipin A Facilitate the Storage of Triacylglycerols J. Biol. Chem., February 27, 2004; 279(9): 8409 - 8416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Ostermeyer, L. T. Ramcharan, Y. Zeng, D. M. Lublin, and D. A. Brown Role of the hydrophobic domain in targeting caveolin-1 to lipid droplets J. Cell Biol., January 5, 2004; 164(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. TASKEN and E. M. AANDAHL Localized Effects of cAMP Mediated by Distinct Routes of Protein Kinase A Physiol Rev, January 1, 2004; 84(1): 137 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Zhang, S. C. Souza, K. V. Muliro, F. B. Kraemer, M. S. Obin, and A. S. Greenberg Lipase-selective Functional Domains of Perilipin A Differentially Regulate Constitutive and Protein Kinase A-stimulated Lipolysis J. Biol. Chem., December 19, 2003; 278(51): 51535 - 51542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sengenes, A. Bouloumie, H. Hauner, M. Berlan, R. Busse, M. Lafontan, and J. Galitzky Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes J. Biol. Chem., December 5, 2003; 278(49): 48617 - 48626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Cohen, T. P. Combs, P. E. Scherer, and M. P. Lisanti Role of caveolin and caveolae in insulin signaling and diabetes Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1151 - E1160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Wolins, J. R. Skinner, M. J. Schoenfish, A. Tzekov, K. G. Bensch, and P. E. Bickel Adipocyte Protein S3-12 Coats Nascent Lipid Droplets J. Biol. Chem., September 26, 2003; 278(39): 37713 - 37721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sztalryd, G. Xu, H. Dorward, J. T. Tansey, J. A. Contreras, A. R. Kimmel, and C. Londos Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation J. Cell Biol., June 23, 2003; 161(6): 1093 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Birnbaum Lipolysis: more than just a lipase J. Cell Biol., June 23, 2003; 161(6): 1011 - 1012. [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 |