GRAF1a is a brain-specific protein that promotes lipid droplet clustering and growth, and is enriched at lipid droplet junctions

Journal of Cell Science

Volumn 127, Issue 21, 2014, Pages 4602-4619

  Häsler, Safa Lucken Ardjomande ^a   Vallis, Yvonne ^a   Jolin, Helen E ^a   McKenzie, Andrew N ^a   McMahon, Harvey T ^a  

^a MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

Author keywords

ARHGAP26; BAR protein; GRAF1; Lipid droplet

Indexed keywords

BRAIN PROTEIN; FAT DROPLET; FATTY ACID; GRAF1A PROTEIN; OLEIC ACID; UNCLASSIFIED DRUG; CARBONIC ACID DERIVATIVE; GRAF1 PROTEIN, MOUSE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; SODIUM CARBONATE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISPERSION; EMBRYO; GENE OVEREXPRESSION; GLIA; GLIA CELL; HOMEOSTASIS; HUMAN; HUMAN CELL; HYDROPHOBICITY; KNOCKOUT MOUSE; LIPOLYSIS; MEMBRANE BINDING; MOUSE; NEWBORN; NONHUMAN; PHENOTYPE; PROTEIN DOMAIN; PROTEIN LOCALIZATION; ANIMAL; BRAIN; CELL CULTURE; CELL FRACTIONATION; DRUG EFFECTS; GENETICS; HELA CELL LINE; METABOLISM; MUTANT MOUSE STRAIN; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; BRAIN; CARBONATES; CELL FRACTIONATION; CELLS, CULTURED; GTPASE-ACTIVATING PROTEINS; HELA CELLS; HUMANS; MICE; MICE, MUTANT STRAINS; NEUROGLIA;

EID: 84913594154     PISSN: 00219533     EISSN: 14779137     Source Type: Journal    
DOI: 10.1242/jcs.147694     Document Type: Article

References (102)

1. Adibhatla, R. M. and Hatcher, J. F. (2007). Role of Lipids in Brain Injury and Diseases. Future Lipidol. 2, 403-422.
2. Andersson, L., Boström, P., Ericson, J., Rutberg, M., Magnusson, B., Marchesan, D., Ruiz, M., Asp, L., Huang, P., Frohman, M. A. et al. (2006). PLD1 and ERK2 regulate cytosolic lipid droplet formation. J. Cell Sci. 119, 2246-2257.
3. Ariotti, N., Murphy, S., Hamilton, N. A., Wu, L., Green, K., Schieber, N. L., Li, P., Martin, S. and Parton, R. G. (2012). Postlipolytic insulin-dependent remodeling of micro lipid droplets in adipocytes. Mol. Biol. Cell 23, 1826-1837.
4. Arisawa, K., Ichi, I., Yasukawa, Y., Sone, Y. and Fujiwara, Y. (2013). Changes in the phospholipid fatty acid composition of the lipid droplet during the differentiation of 3T3-L1 adipocytes. J. Biochem. 154, 281-289.
5. Bai, X., Lenhart, K. C., Bird, K. E., Suen, A. A., Rojas, M., Kakoki, M., Li, F., Smithies, O., Mack, C. P. and Taylor, J. M. (2013). The smooth muscleselective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension. Nat. Commun. 4, 2910.
6. Barba, I., Cabañas, M. E. and Arús, C. (1999). The relationship between nuclear magnetic resonance-visible lipids, lipid droplets, and cell proliferation in cultured C6 cells. Cancer Res. 59, 1861-1868.
7. Barresi, V., Ragusa, A., Fichera, M., Musso, N., Castiglia, L., Rappazzo, G., Travali, S., Mattina, T., Romano, C., Cocchi, G. et al. (2010). Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome. BMC Med. Genomics 3, 28.
8. Bartz, R., Li, W. H., Venables, B., Zehmer, J. K., Roth, M. R., Welti, R., Anderson, R. G., Liu, P. and Chapman, K. D. (2007). Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid traffic. J. Lipid Res. 48, 837-847.
9. Bickel, P. E., Tansey, J. T. and Welte, M. A. (2009). PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim. Biophys. Acta 1791, 419-440.
10. Billuart, P., Bienvenu, T., Ronce, N., des Portes, V., Vinet, M. C., Zemni, R., Roest Crollius, H., Carrié, A., Fauchereau, F., Cherry, M. et al. (1998). Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 392, 923-926.
11. Binns, D., Januszewski, T., Chen, Y., Hill, J., Markin, V. S., Zhao, Y., Gilpin, C., Chapman, K. D., Anderson, R. G. and Goodman, J. M. (2006). An intimate collaboration between peroxisomes and lipid bodies. J. Cell Biol. 173, 719-731.
12. Blouin, C. M., Le Lay, S., Eberl, A., Köfeler, H. C., Guerrera, I. C., Klein, C., Le Liepvre, X., Lasnier, F., Bourron, O., Gautier, J. F. et al. (2010). Lipid droplet analysis in caveolin-deficient adipocytes: alterations in surface phospholipid composition and maturation defects. J. Lipid Res. 51, 945-956.
13. Bojesen, S. E., Ammerpohl, O., Weinhäusl, A., Haas, O. A., Mettal, H., Bohle, R. M., Borkhardt, A. and Fuchs, U. (2006). Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome. Br. J. Cancer 94, 323-332.
14. Borkhardt, A., Bojesen, S., Haas, O. A., Fuchs, U., Bartelheimer, D., Loncarevic, I. F., Bohle, R. M., Harbott, J., Repp, R., Jaeger, U. et al. (2000). The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q. Proc. Natl. Acad. Sci. USA 97, 9168-9173.
15. Boström, P., Rutberg, M., Ericsson, J., Holmdahl, P., Andersson, L., Frohman, M. A., Borén, J. and Olofsson, S. O. (2005). Cytosolic lipid droplets increase in size by microtubule-dependent complex formation. Arterioscler. Thromb. Vasc. Biol. 25, 1945-1951.
16. Brasaemle, D. L. and Wolins, N. E. (2006). Isolation of lipid droplets from cells by density gradient centrifugation. Curr. Protoc. Cell Biol. Chapter 3, Unit 3.15.
17. Brasaemle, D. L. and Wolins, N. E. (2012). Packaging of fat: an evolving model of lipid droplet assembly and expansion. J. Biol. Chem. 287, 2273-2279.
18. Buers, I., Robenek, H., Lorkowski, S., Nitschke, Y., Severs, N. J. and Hofnagel, O. (2009). TIP47, a lipid cargo protein involved in macrophage triglyceride metabolism. Arterioscler. Thromb. Vasc. Biol. 29, 767-773.
19. Bulankina, A. V., Deggerich, A., Wenzel, D., Mutenda, K., Wittmann, J. G., Rudolph, M. G., Burger, K. N. and Höning, S. (2009). TIP47 functions in the biogenesis of lipid droplets. J. Cell Biol. 185, 641-655.
20. Caldas, H. and Herman, G. E. (2003). NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets. Hum. Mol. Genet. 12, 2981-2991.
21. Christianson, J. L., Boutet, E., Puri, V., Chawla, A. and Czech, M. P. (2010). Identification of the lipid droplet targeting domain of the Cidea protein. J. Lipid Res. 51, 3455-3462.
22. Cohen, T., Auerbach, W., Ravid, L., Bodennec, J., Fein, A., Futerman, A. H., Joyner, A. L. and Horowitz, M. (2005). The exon 8-containing prosaposin gene splice variant is dispensable for mouse development, lysosomal function, and secretion. Mol. Cell. Biol. 25, 2431-2440.
23. Cole, N. B., Murphy, D. D., Grider, T., Rueter, S., Brasaemle, D. and Nussbaum, R. L. (2002). Lipid droplet binding and oligomerization properties of the Parkinson's disease protein alpha-synuclein. J. Biol. Chem. 277, 6344-6352.
24. Dupree, P., Parton, R. G., Raposo, G., Kurzchalia, T. V. and Simons, K. (1993). Caveolae and sorting in the trans-Golgi network of epithelial cells. EMBO J. 12, 1597-1605.
25. Eastman, S. W., Yassaee, M. and Bieniasz, P. D. (2009). A role for ubiquitin ligases and Spartin/SPG20 in lipid droplet turnover. J. Cell Biol. 184, 881-894.
26. Ehehalt, R., Füllekrug, J., Pohl, J., Ring, A., Herrmann, T. and Stremmel, W. (2006). Translocation of long chain fatty acids across the plasma membrane -lipid rafts and fatty acid transport proteins. Mol. Cell. Biochem. 284, 135-140.
27. Etschmaier, K., Becker, T., Eichmann, T. O., Schweinzer, C., Scholler, M., Tam-Amersdorfer, C., Poeckl, M., Schuligoi, R., Kober, A., Chirackal Manavalan, A. P. et al. (2011). Adipose triglyceride lipase affects triacylglycerol metabolism at brain barriers. J. Neurochem. 119, 1016-1028.
28. Fei, W., Shui, G., Gaeta, B., Du, X., Kuerschner, L., Li, P., Brown, A. J., Wenk, M. R., Parton, R. G. and Yang, H. (2008). Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. J. Cell Biol. 180, 473-482.
29. Fujimoto, T. and Parton, R. G. (2011). Not just fat: the structure and function of the lipid droplet. Cold Spring Harb. Perspect. Biol. 3, a004838.
30. Fujimoto, T., Kogo, H., Ishiguro, K., Tauchi, K. and Nomura, R. (2001). Caveolin-2 is targeted to lipid droplets, a new ''membrane domain'' in the cell. J. Cell Biol. 152, 1079-1086.
31. Fujimoto, T., Ohsaki, Y., Cheng, J., Suzuki, M. and Shinohara, Y. (2008). Lipid droplets: a classic organelle with new outfits. Histochem. Cell Biol. 130, 263-279.
32. Garcia, A., Sekowski, A., Subramanian, V. and Brasaemle, D. L. (2003). The central domain is required to target and anchor perilipin A to lipid droplets. J. Biol. Chem. 278, 625-635.
33. Gómez-Ramos, P. and Asunción Morán, M. (2007). Ultrastructural localization of intraneuronal Abeta-peptide in Alzheimer disease brains. J. Alzheimers Dis. 11, 53-59.
34. Gong, J., Sun, Z., Wu, L., Xu, W., Schieber, N., Xu, D., Shui, G., Yang, H., Parton, R. G. and Li, P. (2011). Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J. Cell Biol. 195, 953-963.
35. Gross, D. A., Zhan, C. and Silver, D. L. (2011). Direct binding of triglyceride to fat storage-inducing transmembrane proteins 1 and 2 is important for lipid droplet formation. Proc. Natl. Acad. Sci. USA 108, 19581-19586.
36. Hildebrand, J. D., Taylor, J. M. and Parsons, J. T. (1996). An SH3 domaincontaining GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase. Mol. Cell. Biol. 16, 3169-3178.
37. Horiguchi, Y., Araki, M. and Motojima, K. (2008). Identification and characterization of the ER/lipid droplet-targeting sequence in 17betahydroxysteroid dehydrogenase type 11. Arch. Biochem. Biophys. 479, 121-130.
38. Ingelmo-Torres, M., González-Moreno, E., Kassan, A., Hanzal-Bayer, M., Tebar, F., Herms, A., Grewal, T., Hancock, J. F., Enrich, C., Bosch, M. et al. (2009). Hydrophobic and basic domains target proteins to lipid droplets. Traffic 10, 1785-1801.
39. Jambunathan, S., Yin, J., Khan, W., Tamori, Y. and Puri, V. (2011). FSP27 promotes lipid droplet clustering and then fusion to regulate triglyceride accumulation. PLoS ONE 6, e28614.
40. Jarius, S., Wandinger, K. P., Horn, S., Heuer, H. and Wildemann, B. (2010). A new Purkinje cell antibody (anti-Ca) associated with subacute cerebellar ataxia: immunological characterization. J. Neuroinflammation 7, 21.
41. Jarius, S., Martínez-García, P., Hernandez, A. L., Brase, J. C., Borowski, K., Regula, J. U., Meinck, H. M., Stöcker, W., Wildemann, B. and Wandinger, K. P. (2013). Two new cases of anti-Ca (anti-ARHGAP26/GRAF) autoantibodyassociated cerebellar ataxia. J. Neuroinflammation 10, 7.
42. Jiang, W. and Napoli, J. L. (2012). Reorganization of cellular retinol-binding protein type 1 and lecithin:retinol acyltransferase during retinyl ester biosynthesis. Biochim. Biophys. Acta 1820, 859-869.
43. Jiang, W. and Napoli, J. L. (2013). The retinol dehydrogenase Rdh10 localizes to lipid droplets during acyl ester biosynthesis. J. Biol. Chem. 288, 589-597.
44. Jo, Y., Hartman, I. Z. and DeBose-Boyd, R. A. (2013). Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated endoplasmic reticulum membranes. Mol. Biol. Cell 24, 169-183.
45. Kuerschner, L., Ejsing, C. S., Ekroos, K., Shevchenko, A., Anderson, K. I. and Thiele, C. (2005). Polyene-lipids: a new tool to image lipids. Nat. Methods 2, 39-45.
46. Kuerschner, L., Moessinger, C. and Thiele, C. (2008). Imaging of lipid biosynthesis: how a neutral lipid enters lipid droplets. Traffic 9, 338-352.
47. Larigauderie, G., Cuaz-Pérolin, C., Younes, A. B., Furman, C., Lasselin, C., Copin, C., Jaye, M., Fruchart, J. C. and Rouis, M. (2006). Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of beta-oxidation. FEBS J. 273, 3498-3510.
48. Larsson, S., Resjö, S., Gomez, M. F., James, P. and Holm, C. (2012). Characterization of the lipid droplet proteome of a clonal insulin-producing b-cell line (INS-1 832/13). J. Proteome Res. 11, 1264-1273.
49. Lee, J. N., Kim, H., Yao, H., Chen, Y., Weng, K. and Ye, J. (2010). Identification of Ubxd8 protein as a sensor for unsaturated fatty acids and regulator of triglyceride synthesis. Proc. Natl. Acad. Sci. USA 107, 21424-21429.
50. Lemmon, M. A. (2004). Pleckstrin homology domains: not just for phosphoinositides. Biochem. Soc. Trans. 32, 707-711.
51. Liao, J., Sportsman, R., Harris, J. and Stahl, A. (2005). Real-time quantification of fatty acid uptake using a novel fluorescence assay. J. Lipid Res. 46, 597-602.
52. Liu, K., Zhou, S., Kim, J. Y., Tillison, K., Majors, D., Rearick, D., Lee, J. H., Fernandez-Boyanapalli, R. F., Barricklow, K., Houston, M. S. et al. (2009). Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA. Am. J. Physiol. 297, E1395-E1413.
53. Lucken-Ardjomande, S., Montessuit, S. and Martinou, J. C. (2008). Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes. Cell Death Differ. 15, 484-493.
54. Lundmark, R., Doherty, G. J., Howes, M. T., Cortese, K., Vallis, Y., Parton, R. G. and McMahon, H. T. (2008). The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway. Curr. Biol. 18, 1802-1808.
55. Marcinkiewicz, A., Gauthier, D., Garcia, A. and Brasaemle, D. L. (2006). The phosphorylation of serine 492 of perilipin a directs lipid droplet fragmentation and dispersion. J. Biol. Chem. 281, 11901-11909.
56. Martens, S., Kozlov, M. M. and McMahon, H. T. (2007). How synaptotagmin promotes membrane fusion. Science 316, 1205-1208.
57. Martin, S. and Parton, R. G. (2008). Characterization of Rab18, a lipid dropletassociated small GTPase. Methods Enzymol. 438, 109-129.
58. Martin, S., Driessen, K., Nixon, S. J., Zerial, M. and Parton, R. G. (2005). Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. J. Biol. Chem. 280, 42325-42335.
59. McFie, P. J., Banman, S. L., Kary, S. and Stone, S. J. (2011). Murine diacylglycerol acyltransferase-2 (DGAT2) can catalyze triacylglycerol synthesis and promote lipid droplet formation independent of its localization to the endoplasmic reticulum. J. Biol. Chem. 286, 28235-28246.
60. McIntosh, A. L., Storey, S. M. and Atshaves, B. P. (2010). Intracellular lipid droplets contain dynamic pools of sphingomyelin: ADRP binds phospholipids with high affinity. Lipids 45, 465-477.
61. Moessinger, C., Kuerschner, L., Spandl, J., Shevchenko, A. and Thiele, C. (2011). Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine. J. Biol. Chem. 286, 21330-21339.
62. Murphy, S., Martin, S. and Parton, R. G. (2010). Quantitative analysis of lipid droplet fusion: inefficient steady state fusion but rapid stimulation by chemical fusogens. PLoS ONE 5, e15030.
63. Nagato, T. (1993). Lipid droplet accumulation in the exocrine glands of the newborn rat. Okajimas Folia Anat. Jpn. 69, 253-263.
64. Nagato, T. and Masuno, H. (1993). Lipid droplet accumulation and lipoprotein lipase activity in the rat salivary gland during the perinatal period. Arch. Oral Biol. 38, 1127-1134.
65. Nan, X., Potma, E. O. and Xie, X. S. (2006). Nonperturbative chemical imaging of organelle transport in living cells with coherent anti-stokes Raman scattering microscopy. Biophys. J. 91, 728-735.
66. Ohsaki, Y., Maeda, T., Maeda, M., Tauchi-Sato, K. and Fujimoto, T. (2006). Recruitment of TIP47 to lipid droplets is controlled by the putative hydrophobic cleft. Biochem. Biophys. Res. Commun. 347, 279-287.
67. Opstad, K. S., Ladroue, C., Bell, B. A., Griffiths, J. R. and Howe, F. A. (2007). Linear discriminant analysis of brain tumour (1)H MR spectra: a comparison of classification using whole spectra versus metabolite quantification. NMR Biomed. 20, 763-770.
68. Orlicky, D. J., Monks, J., Stefanski, A. L. and McManaman, J. L. (2013). Dynamics and molecular determinants of cytoplasmic lipid droplet clustering and dispersion. PLoS ONE 8, e66837.
69. Ostermeyer, A. G., Ramcharan, L. T., Zeng, Y., Lublin, D. M. and Brown, D. A. (2004). Role of the hydrophobic domain in targeting caveolin-1 to lipid droplets. J. Cell Biol. 164, 69-78.
70. Paglia, G., Ifa, D. R., Wu, C., Corso, G. and Cooks, R. G. (2010). Desorption electrospray ionization mass spectrometry analysis of lipids after twodimensional high-performance thin-layer chromatography partial separation. Anal. Chem. 82, 1744-1750.
71. Penno, A., Hackenbroich, G. and Thiele, C. (2013). Phospholipids and lipid droplets. Biochim. Biophys. Acta 1831, 589-594.
72. Pol, A., Luetterforst, R., Lindsay, M., Heino, S., Ikonen, E. and Parton, R. G. (2001). A caveolin dominant negative mutant associates with lipid bodies and induces intracellular cholesterol imbalance. J. Cell Biol. 152, 1057-1070.
73. Pol, A., Martin, S., Fernandez, M. A., Ferguson, C., Carozzi, A., Luetterforst, R., Enrich, C. and Parton, R. G. (2004). Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell 15, 99-110.
74. Qian, J., Qian, Z., Lin, J., Yao, D. M., Chen, Q., Li, Y., Ji, R. B., Yang, J., Xiao, G. F. and Wang, Y. L. (2011). Abnormal methylation of GRAF promoter Chinese patients with acute myeloid leukemia. Leuk. Res. 35, 783-786.
75. Rémy, C., Fouilhé, N., Barba, I., Sam-Laï, E., Lahrech, H., Cucurella, M. G., Izquierdo, M., Moreno, A., Ziegler, A., Massarelli, R. et al. (1997). Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic resonance correspond to lipid droplets. Cancer Res. 57, 407-414.
76. Shibata, H., Oishi, K., Yamagiwa, A., Matsumoto, M., Mukai, H. and Ono, Y. (2001). PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family. J. Biochem. 130, 23-31.
77. Spandl, J., Lohmann, D., Kuerschner, L., Moessinger, C. and Thiele, C. (2011). Ancient ubiquitous protein 1 (AUP1) localizes to lipid droplets and binds the E2 ubiquitin conjugase G2 (Ube2g2) via its G2 binding region. J. Biol. Chem. 286, 5599-5606.
78. Stevanovic, A. and Thiele, C. (2013). Monotopic topology is required for lipid droplet targeting of ancient ubiquitous protein 1. J. Lipid Res. 54, 503-513.
79. Storey, S. M., McIntosh, A. L., Senthivinayagam, S., Moon, K. C. and Atshaves, B. P. (2011). The phospholipid monolayer associated with perilipinenriched lipid droplets is a highly organized rigid membrane structure. Am. J. Physiol. 301, E991-E1003.
80. Sturley, S. L. and Hussain, M. M. (2012). Lipid droplet formation on opposing sides of the endoplasmic reticulum. J. Lipid Res. 53, 1800-1810.
81. Suzuki, M., Shinohara, Y., Ohsaki, Y. and Fujimoto, T. (2011). Lipid droplets: size matters. J. Electron Microsc. (Tokyo) 60 Suppl. 1, S101-S116.
82. Sztalryd, C., Bell, M., Lu, X., Mertz, P., Hickenbottom, S., Chang, B. H., Chan, L., Kimmel, A. R. and Londos, C. (2006). Functional compensation for adipose differentiation-related protein (ADFP) by Tip47 in an ADFP null embryonic cell line. J. Biol. Chem. 281, 34341-34348.
83. Szymanski, K. M., Binns, D., Bartz, R., Grishin, N. V., Li, W. P., Agarwal, A. K., Garg, A., Anderson, R. G. and Goodman, J. M. (2007). The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc. Natl. Acad. Sci. USA 104, 20890-20895.
84. Targett-Adams, P., Chambers, D., Gledhill, S., Hope, R. G., Coy, J. F., Girod, A. and McLauchlan, J. (2003). Live cell analysis and targeting of the lipid dropletbinding adipocyte differentiation-related protein. J. Biol. Chem. 278, 15998-16007.
85. Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R. and Fujimoto, T. (2002). The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J. Biol. Chem. 277, 44507-44512.
86. Taylor, J. M., Hildebrand, J. D., Mack, C. P., Cox, M. E. and Parsons, J. T. (1998). Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogen-activated protein kinase. J. Biol. Chem. 273, 8063-8070.
87. Taylor, J. M., Macklem, M. M. and Parsons, J. T. (1999). Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho. J. Cell Sci. 112, 231-242.
88. Thiele, C. and Spandl, J. (2008). Cell biology of lipid droplets. Curr. Opin. Cell Biol. 20, 378-385.
89. Turró, S., Ingelmo-Torres, M., Estanyol, J. M., Tebar, F., Fernández, M. A., Albor, C. V., Gaus, K., Grewal, T., Enrich, C. and Pol, A. (2006). Identification and characterization of associated with lipid droplet protein 1: A novel membrane-associated protein that resides on hepatic lipid droplets. Traffic 7, 1254-1269.
90. Wang, H., Wei, E., Quiroga, A. D., Sun, X., Touret, N. and Lehner, R. (2010). Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression. Mol. Biol. Cell 21, 1991-2000.
91. Wang, H., Sreenivasan, U., Hu, H., Saladino, A., Polster, B. M., Lund, L. M., Gong, D. W., Stanley, W. C. and Sztalryd, C. (2011a). Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria. J. Lipid Res. 52, 2159-2168.
92. Wang, H., Zhang, J., Qiu, W., Han, G. S., Carman, G. M. and Adeli, K. (2011b). Lipin-1c isoform is a novel lipid droplet-associated protein highly expressed in the brain. FEBS Lett. 585, 1979-1984.
93. Welte, M. A. (2007). Proteins under new management: lipid droplets deliver. Trends Cell Biol. 17, 363-369.
94. Wilda, M., Perez, A. V., Bruch, J., Woessmann, W., Metzler, M., Fuchs, U. and Borkhardt, A. (2005). Use of MLL/GRAF fusion mRNA for measurement of minimal residual disease during chemotherapy in an infant with acute monoblastic leukemia (AML-M5). Genes Chromosomes Cancer 43, 424-426.
95. Wilfling, F., Wang, H., Haas, J. T., Krahmer, N., Gould, T. J., Uchida, A., Cheng, J. X., Graham, M., Christiano, R., Fröhlich, F. et al. (2013). Triacylglycerol synthesis enzymes mediate lipid droplet growth by relocalizing from the ER to lipid droplets. Dev. Cell 24, 384-399.
96. Wolins, N. E., Quaynor, B. K., Skinner, J. R., Schoenfish, M. J., Tzekov, A. and Bickel, P. E. (2005). S3-12, Adipophilin, and TIP47 package lipid in adipocytes. J. Biol. Chem. 280, 19146-19155.
97. Yang, H., Galea, A., Sytnyk, V. and Crossley, M. (2012). Controlling the size of lipid droplets: lipid and protein factors. Curr. Opin. Cell Biol. 24, 509-516.
98. Zehmer, J. K., Bartz, R., Liu, P. and Anderson, R. G. (2008). Identification of a novel N-terminal hydrophobic sequence that targets proteins to lipid droplets. J. Cell Sci. 121, 1852-1860.
99. Zehmer, J. K., Bartz, R., Bisel, B., Liu, P., Seemann, J. and Anderson, R. G. (2009). Targeting sequences of UBXD8 and AAM-B reveal that the ER has a direct role in the emergence and regression of lipid droplets. J. Cell Sci. 122, 3694-3702.
100. Zhang, H., Wang, Y., Li, J., Yu, J., Pu, J., Li, L., Zhang, H., Zhang, S., Peng, G., Yang, F. et al. (2011). Proteome of skeletal muscle lipid droplet reveals association with mitochondria and apolipoprotein a-I. J. Proteome Res. 10, 4757-4768.
101. Zohrabian, V. M., Nandu, H., Gulati, N., Khitrov, G., Zhao, C., Mohan, A., Demattia, J., Braun, A., Das, K., Murali, R. et al. (2007). Gene expression profiling of metastatic brain cancer. Oncol. Rep. 18, 321-328.
102. Zoula, S., Rijken, P. F., Peters, J. P., Farion, R., Van der Sanden, B. P., Van der Kogel, A. J., Décorps, M. and Rémy, C. (2003). Pimonidazole binding in C6 rat brain glioma: relation with lipid droplet detection. Br. J. Cancer 88, 1439-1444.