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• W2023430066 abstract "The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the body, whereas cholesteryl ester-rich droplets of many other cells provide building materials for local membrane synthesis and repair. These lipid droplets are coated with one or more of five members of the perilipin family of proteins: adipophilin, TIP47, OXPAT/MLDP, S3-12, and perilipin. Members of this family share varying levels of sequence similarity, lipid droplet association, and functions in stabilizing lipid droplets. The most highly studied member of the family, perilipin, is the most abundant protein on the surfaces of adipocyte lipid droplets, and the major substrate for cAMP-dependent protein kinase [protein kinase A (PKA)] in lipolytically stimulated adipocytes. Perilipin serves important functions in the regulation of basal and hormonally stimulated lipolysis. Under basal conditions, perilipin restricts the access of cytosolic lipases to lipid droplets and thus promotes triacylglycerol storage. In times of energy deficit, perilipin is phosphorylated by PKA and facilitates maximal lipolysis by hormone-sensitive lipase and adipose triglyceride lipase. A model is discussed whereby perilipin serves as a dynamic scaffold to coordinate the access of enzymes to the lipid droplet in a manner that is responsive to the metabolic status of the adipocyte. The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the body, whereas cholesteryl ester-rich droplets of many other cells provide building materials for local membrane synthesis and repair. These lipid droplets are coated with one or more of five members of the perilipin family of proteins: adipophilin, TIP47, OXPAT/MLDP, S3-12, and perilipin. Members of this family share varying levels of sequence similarity, lipid droplet association, and functions in stabilizing lipid droplets. The most highly studied member of the family, perilipin, is the most abundant protein on the surfaces of adipocyte lipid droplets, and the major substrate for cAMP-dependent protein kinase [protein kinase A (PKA)] in lipolytically stimulated adipocytes. Perilipin serves important functions in the regulation of basal and hormonally stimulated lipolysis. Under basal conditions, perilipin restricts the access of cytosolic lipases to lipid droplets and thus promotes triacylglycerol storage. In times of energy deficit, perilipin is phosphorylated by PKA and facilitates maximal lipolysis by hormone-sensitive lipase and adipose triglyceride lipase. A model is discussed whereby perilipin serves as a dynamic scaffold to coordinate the access of enzymes to the lipid droplet in a manner that is responsive to the metabolic status of the adipocyte. The ability to synthesize sterol esters or triacylglycerols and store these neutral lipids in cytoplasmic lipid droplets is a universal property of eukaryotes from yeast to humans. Although the presence of lipid droplets in cells and tissues had been noted in early observations of stained histological sections, the elucidation of the functions and composition of lipid droplets is a relatively recent development. Early hypotheses that lipid droplets provide a homeostatic mechanism to regulate intracellular lipid levels date back to studies in the 1970s in the laboratory of Michael S. Brown and Joseph L. Goldstein showing the esterification of cholesterol derived from the receptor-mediated uptake of low density lipoproteins and the depletion of cholesteryl ester stores after the withdrawal of lipoproteins from the culture medium of cells (1Brown M.S. Faust J.R. Goldstein J.L. Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.J. Clin. Invest. 1975; 55: 783-793Crossref PubMed Google Scholar, 2Brown M.S. Goldstein J.L. Receptor-mediated control of cholesterol metabolism.Science. 1976; 191: 150-154Crossref PubMed Google Scholar, 3Goldstein J.L. Dana S.E. Brown M.S. Esterification of low density lipoprotein cholesterol in human fibroblasts and its absence in homozygous familial hypercholesterolemia.Proc. Natl. Acad. Sci. USA. 1974; 71: 4288-4292Crossref PubMed Google Scholar). Despite early speculation that cytosolic lipid droplets provide an important source of cholesterol for the maintenance, repair, and synthesis of membranes, very few studies throughout the 1970s and 1980s addressed the formation or dissolution of lipid droplets. The first hint that proteins coat the cytosolic surfaces of intracellular lipid droplets and play critical roles in regulating neutral lipid metabolism emerged with the discovery of perilipins on adipocyte lipid droplets in the laboratory of Constantine Londos in 1991 (4Greenberg A.S. Egan J.J. Wek S.A. Garty N.B. Blanchette-Mackie E.J. Londos C. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets.J. Biol. Chem. 1991; 266: 11341-11346Abstract Full Text PDF PubMed Google Scholar). Since the identification of perilipins, four additional lipid droplet proteins with sequence similarity to perilipins have been described in vertebrates, with two additional family members in insects; these proteins include adipophilin (also called adipose differentiation-related protein), TIP47 (for Tail-Interacting Protein of 47 kDa), S3-12, OXPAT (also called Myocardial Lipid Droplet Protein or MLDP and Lipid Storage Droplet Protein 5 or LSDP5), and LSD1 and LSD2 (for Lipid Storage Droplet proteins 1 and 2) in vertebrates and insects, respectively. These proteins constitute the most abundant structural proteins on lipid droplets. Recent proteomics analyses have identified numerous enzymes involved in lipid metabolism and membrane trafficking on lipid droplets isolated from cultured mammalian cells or tissues (5Brasaemle D.L. Dolios G. Shapiro L. Wang R. Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes.J. Biol. Chem. 2004; 279: 46835-46842Abstract Full Text Full Text PDF PubMed Scopus (591) Google Scholar, 6Fujimoto Y. Itabe H. Sakai J. Makita M. Noda J. Mori M. Higashi Y. Kojima S. Takano T. Identification of major proteins in the lipid droplet-enriched fraction isolated from the human hepatocyte cell line HuH7.Biochim. Biophys. Acta. 2004; 1644: 47-59Crossref PubMed Scopus (255) Google Scholar, 7Liu P. Ying Y. Zhao Y. Mundy D.I. Zhu M. Anderson R.G. Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic.J. Biol. Chem. 2004; 279: 3787-3792Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 8Turro S. Ingelmo-Torres M. Estanyol J.M. Tebar F. Fernandez M.A. Albor C.V. Gaus K. Grewal T. Enrich C. Pol A. Identification and characterization of associated with lipid droplet protein 1: a novel membrane-associated protein that resides on hepatic lipid droplets.Traffic. 2006; 7: 1254-1269Crossref PubMed Scopus (143) Google Scholar, 9Umlauf E. Csaszar E. Moertelmaier M. Schuetz G.J. Parton R.G. Prohaska R. Association of stomatin with lipid bodies.J. Biol. Chem. 2004; 279: 23699-23709Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar, 10Wu C.C. Howell K.E. Neville M.C. Yates III, J.R. McManaman J.L. Proteomics reveal a link between the endoplasmic reticulum and lipid secretory mechanisms in mammary epithelial cells.Electrophoresis. 2000; 21: 3470-3482Crossref PubMed Scopus (182) Google Scholar); investigations of the localization of various newly identified proteins in cultured cells have further defined the lipid droplet as a distinct subcellular compartment or organelle. In the past few years, interest in the biology of lipid droplets has increased rapidly (11Beckman M. Cell biology. Great balls of fat.Science. 2006; 311: 1232-1234Crossref PubMed Scopus (76) Google Scholar); the lipid droplet is now recognized as a dynamic organelle with a distinct lipid and protein composition and important functions in the maintenance of cellular lipid homeostasis, energy storage, and the production of signaling lipids. Lipid droplets in plants have classically been termed oil bodies. The study of proteins associated with oil bodies in the seeds of plants began in the 1970s and 1980s, with the first full-length sequence of an oleosin described in 1990 (12Qu R.D. Huang A.H. Oleosin KD 18 on the surface of oil bodies in maize. Genomic and cDNA sequences and the deduced protein structure.J. Biol. Chem. 1990; 265: 2238-2243Abstract Full Text PDF PubMed Google Scholar); these low molecular weight proteins are integral components of plant oil bodies without apparent homologs in vertebrates. Discussion of the biology of plant lipid droplets (13Hsieh K. Huang A.H. Endoplasmic reticulum, oleosins, and oils in seeds and tapetum cells.Plant Physiol. 2004; 136: 3427-3434Crossref PubMed Scopus (149) Google Scholar), as well as a rapidly growing literature on yeast lipid droplets (reviewed recently in Ref. 14Czabany T. Athenstaedt K. Daum G. Synthesis, storage and degradation of neutral lipids in yeast.Biochim. Biophys. Acta. 2007; 1771: 299-309Crossref PubMed Scopus (169) Google Scholar), are beyond the scope of this discussion, which will focus on building a model for how perilipin and related structural lipid droplet-associated proteins function to regulate the metabolism of triacylglycerols. A cytosolic lipid droplet has a comparable micellar structure to a serum lipoprotein. In the majority of cells, the neutral lipid core contains triacylglycerols and cholesteryl esters; in some types of cells, the core may also store retinol esters or ether lipids of the monoalkyl or monoalkenyl diacylglycerol classes (15Bartz R. Li W.H. Venables B. Zehmer J.K. Roth M.R. Welti R. Anderson R.G. Liu P. Chapman K.D. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic.J. Lipid Res. 2007; 48: 837-847Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar). The triacylglycerol-rich lipid droplets of adipocytes provide the largest storage depot for energy in the form of esterified fatty acids that are mobilized to skeletal muscle and other tissues of the body for metabolism through β-oxidation to support ATP production. Lipolysis of adipocyte triacylglycerol also releases glycerol that is transported to liver for metabolism by either gluconeogenesis or glycolysis. Many other types of cells have cholesteryl ester-enriched lipid droplets that provide a source of cholesterol for membrane synthesis and repair; additionally, steroidogenic cells of the adrenal cortex, testes, and ovaries used stored cholesteryl esters as a source of substrate for steroid hormone synthesis (16Bisgaier C.L. Chanderbhan R. Hinds R.W. Vahouny G.V. Adrenal cholesterol esters as substrate source for steroidogenesis.J. Steroid Biochem. 1985; 23: 967-974Crossref PubMed Scopus (27) Google Scholar, 17Freeman D.A. Ascoli M. Studies on the source of cholesterol used for steroid biosynthesis in cultured Leydig tumor cells.J. Biol. Chem. 1982; 257: 14231-14238Abstract Full Text PDF PubMed Google Scholar, 18Gwynne J.T. Strauss III, J.F. The role of lipoproteins in steroidogenesis and cholesterol metabolism in steroidogenic glands.Endocr. Rev. 1982; 3: 299-329Crossref PubMed Google Scholar, 19Nagy L. Freeman D.A. Effect of cholesterol transport inhibitors on steroidogenesis and plasma membrane cholesterol transport in cultured MA-10 Leydig tumor cells.Endocrinology. 1990; 126: 2267-2276Crossref PubMed Google Scholar). Lipid droplets within the stellate cells of liver have a uniquely high content of retinol esters that can be mobilized for use by cells throughout the body (20Senoo H. Structure and function of hepatic stellate cells.Med. Electron Microsc. 2004; 37: 3-15Crossref PubMed Scopus (169) Google Scholar). Specialized interstitial cells within the lung, termed lipofibroblasts, store triacylglycerols that are metabolized to provide substrate for the synthesis of surfactant phospholipids in type II alveolar epithelial cells (21McGowan S.E. Torday J.S. The pulmonary lipofibroblast (lipid interstitial cell) and its contributions to alveolar development.Annu. Rev. Physiol. 1997; 59: 43-62Crossref PubMed Scopus (151) Google Scholar). Additionally, secretory epithelial cells in the mammary gland extrude cytosolic triacylglycerol-rich lipid droplets across the apical membranes to supply the lipid component of milk (22McManaman J.L. Reyland M.E. Thrower E.C. Secretion and fluid transport mechanisms in the mammary gland: comparisons with the exocrine pancreas and the salivary gland.J. Mammary Gland Biol. Neoplasia. 2006; 11: 249-268Crossref PubMed Scopus (49) Google Scholar). Finally, lipid droplets provide substrates for the synthesis of signaling lipids and mediators of inflammation in leukocytes and other types of cells (23Bozza P.T. Melo R.C. Bandeira-Melo C. Leukocyte lipid bodies regulation and function: contribution to allergy and host defense.Pharmacol. Ther. 2007; 113: 30-49Crossref PubMed Scopus (84) Google Scholar). The core lipid is surrounded by a phospholipid monolayer (24Blanchette-Mackie E.J. Dwyer N.K. Barber T. Coxey R.A. Takeda T. Rondinone C.M. Theodorakis J.L. Greenberg A.S. Londos C. Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes.J. Lipid Res. 1995; 36: 1211-1226Abstract Full Text PDF PubMed Google Scholar, 25Tauchi-Sato K. Ozeki S. Houjou T. Taguchi R. Fujimoto T. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.J. Biol. Chem. 2002; 277: 44507-44512Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar) containing cholesterol into which specific proteins may be embedded or peripherally associated through electrostatic interactions. The phospholipid composition of lipid droplets from several types of cells has been characterized; phosphatidyl choline is the most abundant phospholipid (15Bartz R. Li W.H. Venables B. Zehmer J.K. Roth M.R. Welti R. Anderson R.G. Liu P. Chapman K.D. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic.J. Lipid Res. 2007; 48: 837-847Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar, 25Tauchi-Sato K. Ozeki S. Houjou T. Taguchi R. Fujimoto T. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.J. Biol. Chem. 2002; 277: 44507-44512Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar), followed by phosphatidyl ethanolamine, phosphatidyl inositol, ether-linked phosphatidyl choline and phosphatidyl ethanolamine, and lysophosphatidyl choline and lysophosphatidyl ethanolamine, with very low levels of sphingomyelin, phosphatidic acid, and phosphatidyl serine (15Bartz R. Li W.H. Venables B. Zehmer J.K. Roth M.R. Welti R. Anderson R.G. Liu P. Chapman K.D. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic.J. Lipid Res. 2007; 48: 837-847Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar). Importantly, the relative content of specific phospholipids, as well as the acyl chain composition of the phospholipids on lipid droplets, differs from that of bulk membranes or microsomes; the acyl chains are more highly unsaturated (15Bartz R. Li W.H. Venables B. Zehmer J.K. Roth M.R. Welti R. Anderson R.G. Liu P. Chapman K.D. Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic.J. Lipid Res. 2007; 48: 837-847Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar, 25Tauchi-Sato K. Ozeki S. Houjou T. Taguchi R. Fujimoto T. The surface of lipid droplets is a phospholipid monolayer with a unique fatty acid composition.J. Biol. Chem. 2002; 277: 44507-44512Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar), suggesting potentially unique origins and functions of lipid droplet phospholipids. The lipid droplets of cells from vertebrates contain one or more of five related structural proteins: perilipin, adipophilin, TIP47, S3-12, and OXPAT/MLDP (Fig. 1). Collectively, these proteins have been referred to in the literature as the PAT family of proteins, named after Perilipin, Adipophilin, and TIP47. Adipophilin (26Brasaemle D.L. Barber T. Wolins N.E. Serrero G. Blanchette-Mackie E.J. Londos C. Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein.J. Lipid Res. 1997; 38: 2249-2263Abstract Full Text PDF PubMed Google Scholar, 27Heid H.W. Moll R. Schwetlick I. Rackwitz H.R. Keenan T.W. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases.Cell Tissue Res. 1998; 294: 309-321Crossref PubMed Scopus (334) Google Scholar) and TIP47 (28Diaz E. Pfeffer S.R. TIP47: a cargo selection device for mannose 6-phosphate receptor trafficking.Cell. 1998; 93: 433-443Abstract Full Text Full Text PDF PubMed Scopus (308) Google Scholar, 29Miura S. Gan J.W. Brzostowski J. Parisi M.J. Schultz C.J. Londos C. Oliver B. Kimmel A.R. Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium.J. Biol. Chem. 2002; 277: 32253-32257Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar, 30Wolins N.E. Rubin B. Brasaemle D.L. TIP47 associates with lipid droplets.J. Biol. Chem. 2001; 276: 5101-5108Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar) are expressed in the majority of cells and share the highest identity (43%) between amino acid sequences. Whereas adipophilin localizes exclusively to lipid droplets (26Brasaemle D.L. Barber T. Wolins N.E. Serrero G. Blanchette-Mackie E.J. Londos C. Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein.J. Lipid Res. 1997; 38: 2249-2263Abstract Full Text PDF PubMed Google Scholar, 27Heid H.W. Moll R. Schwetlick I. Rackwitz H.R. Keenan T.W. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases.Cell Tissue Res. 1998; 294: 309-321Crossref PubMed Scopus (334) Google Scholar), TIP47 is stable both as a soluble cytosolic protein and when associated with lipid droplets (29Miura S. Gan J.W. Brzostowski J. Parisi M.J. Schultz C.J. Londos C. Oliver B. Kimmel A.R. Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium.J. Biol. Chem. 2002; 277: 32253-32257Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar, 30Wolins N.E. Rubin B. Brasaemle D.L. TIP47 associates with lipid droplets.J. Biol. Chem. 2001; 276: 5101-5108Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 31Than N.G. Sumegi B. Bellyei S. Berki T. Szekeres G. Janaky T. Szigeti A. Bohn H. Than G.N. Lipid droplet and milk lipid globule membrane associated placental protein 17b (PP17b) is involved in apoptotic and differentiation processes of human epithelial cervical carcinoma cells.Eur. J. Biochem. 2003; 270: 1176-1188Crossref PubMed Scopus (52) Google Scholar, 32Wolins N.E. Quaynor B.K. Skinner J.R. Schoenfish M.J. Tzekov A. Bickel P.E. S3-12, adipophilin, and TIP47 package lipid in adipocytes.J. Biol. Chem. 2005; 280: 19146-19155Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar). The crystal structure of the C-terminal 60% of TIP47 (33Hickenbottom S.J. Kimmel A.R. Londos C. Hurley J.H. Structure of a lipid droplet protein: the PAT family member TIP47.Structure. 2004; 12: 1199-1207Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar) reveals clues that may explain this dual localization: four amphipathic helices form a bundle in solution that is similar to the four helix bundle of the N terminus of lipid-free apolipoprotein E, an exchangeable apolipoprotein. Although lipid-free apolipoprotein E is stable in solution and circulates in the blood, biophysical studies show that the four helix bundle of apolipoprotein E opens during lipid binding to embed the hydrophobic surfaces of the helices into the acyl chains of the surface phospholipid monolayer of lipoproteins (34Hatters D.M. Peters-Libeu C.A. Weisgraber K.H. Apolipoprotein E structure: insights into function.Trends Biochem. Sci. 2006; 31: 445-454Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar, 35Saito H. Lund-Katz S. Phillips M.C. Contributions of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins.Prog. Lipid Res. 2004; 43: 350-380Crossref PubMed Scopus (175) Google Scholar). Similarly, TIP47 is rapidly recruited from the cytosol to nascent lipid droplets when cells are provided with fatty acid substrates for triacylglycerol synthesis and storage (30Wolins N.E. Rubin B. Brasaemle D.L. TIP47 associates with lipid droplets.J. Biol. Chem. 2001; 276: 5101-5108Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 32Wolins N.E. Quaynor B.K. Skinner J.R. Schoenfish M.J. Tzekov A. Bickel P.E. S3-12, adipophilin, and TIP47 package lipid in adipocytes.J. Biol. Chem. 2005; 280: 19146-19155Abstract Full Text Full Text PDF PubMed Scopus (252) Google Scholar); thus, opening of the four helix bundle may facilitate TIP47 binding to lipid droplets, which, in turn, may stabilize the newly formed lipid droplets (36Wolins N.E. Brasaemle D.L. Bickel P.E. A proposed model of fat packaging by exchangeable lipid droplet proteins.FEBS Lett. 2006; 580: 5484-5491Crossref PubMed Scopus (295) Google Scholar). Alignment of the adipophilin amino acid sequence with that of TIP47 shows significant sequence similarity (33Hickenbottom S.J. Kimmel A.R. Londos C. Hurley J.H. Structure of a lipid droplet protein: the PAT family member TIP47.Structure. 2004; 12: 1199-1207Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar), suggesting that the C terminus of adipophilin may also fold into a series of four amphipathic helices; however, adipophilin is highly unstable in the cytoplasm and is subject to rapid proteasome-mediated degradation (37Gross D.N. Miyoshi H. Hosaka T. Zhang H.H. Pino E.C. Souza S. Obin M. Greenberg A.S. Pilch P.F. 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. 2006; 20: 459-466Crossref PubMed Scopus (43) Google Scholar, 38Masuda Y. Itabe H. Odaki M. Hama K. Fujimoto Y. Mori M. Sasabe N. Aoki J. Arai H. Takano T. ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells.J. Lipid Res. 2006; 47: 87-98Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar, 39Xu G. Sztalryd C. Lu X. Tansey J.T. Gan J. Dorward H. Kimmel A.R. Londos C. Post-translational regulation of adipose differentiation-related protein by the ubiquitin/proteasome pathway.J. Biol. Chem. 2005; 280: 42841-42847Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar). Thus, significant variation in the amino acid sequence of adipophilin may alter the structure to prevent closure of the four helix bundle and the dissociation of adipophilin from the surfaces of lipid droplets to fold into a stable soluble protein. Interestingly, published deletion mutagenesis studies for TIP47 (40Ohsaki Y. Maeda T. Maeda M. Tauchi-Sato K. Fujimoto T. Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic cleft.Biochem. Biophys. Res. Commun. 2006; 347: 279-287Crossref PubMed Scopus (48) Google Scholar) and adipophilin (41McManaman J.L. Zabaronick W. Schaack J. Orlicky D.J. Lipid droplet targeting domains of adipophilin.J. Lipid Res. 2003; 44: 668-673Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar, 42Nakamura N. Fujimoto T. Adipose differentiation-related protein has two independent domains for targeting to lipid droplets.Biochem. Biophys. Res. Commun. 2003; 306: 333-338Crossref PubMed Scopus (60) Google Scholar, 43Targett-Adams P. Chambers D. Gledhill S. Hope R.G. Coy J.F. Girod A. McLauchlan J. Live cell analysis and targeting of the lipid droplet-binding adipocyte differentiation-related protein.J. Biol. Chem. 2003; 278: 15998-16007Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar) reveal that sequences predicted to form these four helices are insufficient to direct the targeting of either nascent protein to lipid droplets. However, a natural splice variant of TIP47 mRNA produces a truncated form of the protein in human steroidogenic cells that includes the four helix bundle sequence but lacks the majority of N-terminal amino acids (44Than N.G. Sumegi B. Than G.N. Kispal G. Bohn H. Cloning and sequence analysis of cDNAs encoding human placental tissue protein 17 (PP17) variants.Eur. J. Biochem. 1998; 258: 752-757Crossref PubMed Scopus (37) Google Scholar); this alternative form of TIP47 reportedly associates with lipid droplets (31Than N.G. Sumegi B. Bellyei S. Berki T. Szekeres G. Janaky T. Szigeti A. Bohn H. Than G.N. Lipid droplet and milk lipid globule membrane associated placental protein 17b (PP17b) is involved in apoptotic and differentiation processes of human epithelial cervical carcinoma cells.Eur. J. Biochem. 2003; 270: 1176-1188Crossref PubMed Scopus (52) Google Scholar). The most recently described member of the perilipin family has been given several names, including OXPAT (for a PAT family protein expressed in oxidative tissues) (45Wolins N.E. Quaynor B.K. Skinner J.R. Tzekov A. Croce M.A. Gropler M.C. Varma V. Yao-Borengasser A. Rasouli N. Kern P.A. et al.OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.Diabetes. 2006; 55: 3418-3428Crossref PubMed Scopus (219) Google Scholar), MLDP (46Yamaguchi T. Matsushita S. Motojima K. Hirose F. Osumi T. MLDP, a novel PAT family protein localized to lipid droplets and enriched in the heart, is regulated by peroxisome proliferator-activated receptor alpha.J. Biol. Chem. 2006; 281: 14232-14240Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar), and LSDP5 (47Dalen K.T. Dahl T. Holter E. Arntsen B. Londos C. Sztalryd C. Nebb H.I. LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues.Biochim. Biophys. Acta. 2007; 1771: 210-227Crossref PubMed Scopus (163) Google Scholar). OXPAT/MLDP is most highly expressed in heart and slow-twitch muscle, with lower levels in fast-twitch muscle, liver, white and brown adipose tissue, testis, and adrenal gland (45Wolins N.E. Quaynor B.K. Skinner J.R. Tzekov A. Croce M.A. Gropler M.C. Varma V. Yao-Borengasser A. Rasouli N. Kern P.A. et al.OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.Diabetes. 2006; 55: 3418-3428Crossref PubMed Scopus (219) Google Scholar, 46Yamaguchi T. Matsushita S. Motojima K. Hirose F. Osumi T. MLDP, a novel PAT family protein localized to lipid droplets and enriched in the heart, is regulated by peroxisome proliferator-activated receptor alpha.J. Biol. Chem. 2006; 281: 14232-14240Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar, 47Dalen K.T. Dahl T. Holter E. Arntsen B. Londos C. Sztalryd C. Nebb H.I. LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues.Biochim. Biophys. Acta. 2007; 1771: 210-227Crossref PubMed Scopus (163) Google Scholar). OXPAT/MLDP is related to TIP47 (30% identity) and adipophilin (26% identity) throughout the amino acid sequence (45Wolins N.E. Quaynor B.K. Skinner J.R. Tzekov A. Croce M.A. Gropler M.C. Varma V. Yao-Borengasser A. Rasouli N. Kern P.A. et al.OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.Diabetes. 2006; 55: 3418-3428Crossref PubMed Scopus (219) Google Scholar). Furthermore, like TIP47, OXPAT/MLDP is stable in the cytoplasm but is recruited to lipid droplets under conditions that promote lipid droplet formation (45Wolins N.E. Quaynor B.K. Skinner J.R. Tzekov A. Croce M.A. Gropler M.C. Varma V. Yao-Borengasser A. Rasouli N. Kern P.A. et al.OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.Diabetes. 2006; 55: 3418-3428Crossref PubMed Scopus (219) Google Scholar). The two remaining members of the protein family, perilipin and S3-12, have divergent amino acid sequences relative to TIP47, adipophilin, OXPAT/MLDP, and each other (Fig. 1). They also show limited tissue distribution. S3-12 expression is highest in white adipocytes, with very low expression in heart and skeletal muscle and little or no expression in brown adipocytes (48Scherer P.E. Bickel P.E. Kotler M. Lodish H.F. Cloning of cell-specific secreted and surface proteins by subtractive antibody screening.Nat. Biotechnol. 1998; 16: 581-586Crossref PubMed Scopus (102) Google Scholar, 49Wolins N.E. Skinner J.R. Schoenfish M.J. Tzekov A. Bensch K.G. Bickel P.E. Adipocyte protein s3-12 coats nascent lipid droplets.J. Biol. Chem. 2003; 278: 37713-37721Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar). Perilipin expression is highest in white and brown adipocytes (4Greenberg A.S. Egan J.J. Wek S.A. Garty N.B. Blanchette-Mackie E.J. Londos C. Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets.J. Biol. Chem. 1991; 266: 11341-11346Abstract Full Text PDF PubMed Google Scholar, 50Greenberg A.S. Egan J.J. Wek S.A. Moos Jr, M.C. Londos C. Kimmel A.R. Isolation of cDNAs for perilipins A and B: sequence and expression of lipid droplet-associated proteins of" @default.
• W2023430066 created "2016-06-24" @default.
• W2023430066 creator A5085628480 @default.
• W2023430066 date "2007-12-01" @default.
• W2023430066 modified "2023-10-16" @default.
• W2023430066 title "Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis" @default.
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