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Licensed Unlicensed Requires Authentication Published by De Gruyter September 13, 2016

A role for the metalloprotease invadolysin in insulin signaling and adipogenesis

Ching-Wen Chang , Kanishk Abhinav , Francesca Di Cara , Ioanna Panagakou , Sharron Vass and Margarete M.S. Heck EMAIL logo
From the journal Biological Chemistry

Abstract

Invadolysin is a novel metalloprotease conserved amongst metazoans that is essential for life in Drosophila. We previously showed that invadolysin was essential for the cell cycle and cell migration, linking to metabolism through a role in lipid storage and interaction with mitochondrial proteins. In this study we demonstrate that invadolysin mutants exhibit increased autophagy and decreased glycogen storage – suggestive of a role for invadolysin in insulin signaling in Drosophila. Consistent with this, effectors of insulin signaling were decreased in invadolysin mutants. In addition, we discovered that invadolysin was deposited on newly synthesized lipid droplets in a PKC-dependent manner. We examined two in vitro models of adipogenesis for the expression and localization of invadolysin. The level of invadolysin increased during both murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS), adipogenesis. Invadolysin displayed a dynamic localization to lipid droplets over the course of adipogenesis, which may be due to the differential expression of distinct invadolysin variants. Pharmacological inhibition of adipogenesis abrogated the increase in invadolysin. In summary, our results on in vivo and in vitro systems highlight an important role for invadolysin in insulin signaling and adipogenesis.

References

Accioly, M.T., Pacheco, P., Maya-Monteiro, C.M., Carrossini, N., Robbs, B.K., Oliveira, S.S., Kaufmann, C., Morgado-Diaz, J.A., Bozza, P.T., and Viola, J.P. (2008). Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells. Cancer Res. 68, 1732–1740.10.1158/0008-5472.CAN-07-1999Search in Google Scholar

Akimoto, N., Sato, T., Iwata, C., Koshizuka, M., Shibata, F., Nagai, A., Sumida, M., and Ito, A. (2005). Expression of perilipin A on the surface of lipid droplets increases along with the differentiation of hamster sebocytes in vivo and in vitro. J. Invest. Dermatol. 124, 1127–1133.10.1111/j.0022-202X.2005.23718.xSearch in Google Scholar

Andersson, L., Bostrom, 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, 2246–2257.10.1242/jcs.02941Search in Google Scholar

Arimura, N., Horiba, T., Imagawa, M., Shimizu, M., and Sato, R. (2004). The peroxisome proliferator-activated receptor g regulates expression of the perilipin gene in adipocytes. J. Biol. Chem. 279, 10070–10076.10.1074/jbc.M308522200Search in Google Scholar

Aubin, D., Gagnon, A., and Sorisky, A. (2005). Phosphoinositide 3-kinase is required for human adipocyte differentiation in culture. Int. J. Obes. (Lond.) 29, 1006–1009.10.1038/sj.ijo.0802961Search in Google Scholar

Barak, Y., Nelson, M.C., Ong, E.S., Jones, Y.Z., Ruiz-Lozano, P., Chien, K.R., Koder, A., and Evans, R.M. (1999). PPARg is required for placental, cardiac, and adipose tissue development. Mol. Cell 4, 585–595.10.1016/S1097-2765(00)80209-9Search in Google Scholar

Bartz, R., Zehmer, J.K., Zhu, M., Chen, Y., Serrero, G., Zhao, Y., and Liu, P. (2007). Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. J. Proteome. Res. 6, 3256–3265.10.1021/pr070158jSearch in Google Scholar PubMed

Blom, N., Gammeltoft, S., and Brunak, S. (1999). Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol. 294, 1351–1362.10.1006/jmbi.1999.3310Search in Google Scholar PubMed

Blom, N., Sicheritz-Pontén, T., Gupta, R., Gammeltoft, S., and Brunak, S. (2004). Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4, 1633–1649.10.1002/pmic.200300771Search in Google Scholar PubMed

Blouin, C.M., Le Lay, S., Lasnier, F., Dugail, I., and Hajduch, E. (2008). Regulated association of caveolins to lipid droplets during differentiation of 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 376, 331–335.10.1016/j.bbrc.2008.08.154Search in Google Scholar PubMed

Brasaemle, D.L., Dolios, G., Shapiro, L., and Wang, R. (2004). Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. J. Biol. Chem. 279, 46835–46842.10.1074/jbc.M409340200Search in Google Scholar PubMed

Cermelli, S., Guo, Y., Gross, S.P., and Welte, M.A. (2006). The lipid-droplet proteome reveals that droplets are a protein-storage depot. Curr. Biol. 16, 1783–1795.10.1016/j.cub.2006.07.062Search in Google Scholar PubMed

Chen, J.S., Greenberg, A.S., and Wang, S.M. (2002). Oleic acid-induced PKC isozyme translocation in RAW 264.7 macrophages. J. Cell Biochem. 86, 784–791.10.1002/jcb.10266Search in Google Scholar PubMed

Chikte, S., Panchal, N., and Warnes, G. (2014). Use of LysoTracker dyes: a flow cytometric study of autophagy. Cytometry A 85, 169–178.10.1002/cyto.a.22312Search in Google Scholar PubMed

Cobbe, N., Marshall, K.M., Gururaja Rao, S., Chang, C.W., Di Cara, F., Duca, E., Vass, S., Kassan, A., and Heck, M.M. (2009). The conserved metalloprotease invadolysin localizes to the surface of lipid droplets. J. Cell Sci. 122, 3414–3423.10.1242/jcs.044610Search in Google Scholar PubMed PubMed Central

Di Cara, F., Duca, E., Dunbar, D.R., Cagney, G., and Heck, M.M. (2013). Invadolysin, a conserved lipid-droplet-associated metalloproteinase, is required for mitochondrial function in Drosophila. J. Cell Sci. 126, 4769–4781.Search in Google Scholar

Eberlé, D., Hegarty, B., Bossard, P., Ferré, P., and Foufelle, F. (2004). SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86, 839–848.10.1016/j.biochi.2004.09.018Search in Google Scholar PubMed

El-Chaâr, D., Gagnon, A., and Sorisky, A. (2004). Inhibition of insulin signaling and adipogenesis by rapamycin: effect on phosphorylation of p70 S6 kinase vs eIF4E-BP1. Int. J. Obes. Relat. Metab. Disord. 28, 191–198.10.1038/sj.ijo.0802554Search in Google Scholar PubMed

Farmer, S.R. (2006). Transcriptional control of adipocyte formation. Cell Metab. 4, 263–273.10.1016/j.cmet.2006.07.001Search in Google Scholar PubMed PubMed Central

Fingar, D.C. and Blenis, J. (2004). Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23, 3151–3171.10.1038/sj.onc.1207542Search in Google Scholar PubMed

Fischer-Posovszky, P., Newell, F.S., Wabitsch, M., and Tornqvist, H.E. (2008). Human SGBS cells-a unique tool for studies of human fat cell biology. Obes. Facts 1, 184–189.10.1159/000145784Search in Google Scholar PubMed PubMed Central

Fleming, I., MacKenzie, S.J., Vernon, R.G., Anderson, N.G., Houslay, M.D., and Kilgour, E. (1998). Protein kinase C isoforms play differential roles in the regulation of adipocyte differentiation. Biochem. J. 333, 719–727.10.1042/bj3330719Search in Google Scholar

Garofalo, R.S. (2002). Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol. Metab. 13, 156–162.10.1016/S1043-2760(01)00548-3Search in Google Scholar

Goldberg, A.A., Bourque, S.D., Kyryakov, P., Boukh-Viner, T., Gregg, C., Beach, A., Burstein, M.T., Machkalyan, G., Richard, V., Rampersad, S., et al. (2009). A novel function of lipid droplets in regulating longevity. Biochem. Soc. Trans. 37, 1050–1055.10.1042/BST0371050Search in Google Scholar

Gomis-Ruth, F.X. (2003). Structural aspects of the metzincin clan of metalloendopeptidases. Mol. Biotechnol. 24, 157–202.10.1385/MB:24:2:157Search in Google Scholar

Green, H. and Kehinde, O. (1976). Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 7, 105–113.10.1016/0092-8674(76)90260-9Search in Google Scholar

Halse, R., Bonavaud, S.M., Armstrong, J.L., McCormack, J.G., and Yeaman, S.J. (2001). Control of glycogen synthesis by glucose, glycogen, and insulin in cultured human muscle cells. Diabetes 50, 720–726.10.2337/diabetes.50.4.720Search in Google Scholar

Holm, C. (2003). Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem. Soc. Trans. 31, 1120–1124.10.1042/bst0311120Search in Google Scholar PubMed

Imamura, M., Inoguchi, T., Ikuyama, S., Taniguchi, S., Kobayashi, K., Nakashima, N., and Nawata, H. (2002). ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts. Am. J. Physiol. Endocrinol. Metab. 283, E775–783.10.1152/ajpendo.00040.2002Search in Google Scholar PubMed

Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K.L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4, 648–657.10.1038/ncb839Search in Google Scholar PubMed

Jung, C.H., Ro, S.H., Cao, J., Otto, N.M., and Kim, D.H. (2010). mTOR regulation of autophagy. FEBS Lett. 584, 1287–1295.10.1016/j.febslet.2010.01.017Search in Google Scholar PubMed PubMed Central

Kim, J.E. and Chen, J. (2004). regulation of peroxisome proliferator-activated receptor- g activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes 53, 2748–2756.10.2337/diabetes.53.11.2748Search in Google Scholar

Lawrence, J.C., Lin, T.A., McMahon, L.P., and Choi, K.M. (2004). Modulation of the protein kinase activity of mTOR. Curr. Top Microbiol. Immunol. 279, 199–213.10.1007/978-3-642-18930-2_12Search in Google Scholar

Le Lay, S., Hajduch, E., Lindsay, M.R., Le Lièpvre, X., Thiele, C., Ferré, P., Parton, R.G., Kurzchalia, T., Simons, K., and Dugail, I. (2006). Cholesterol-induced caveolin targeting to lipid droplets in adipocytes: a role for caveolar endocytosis. Traffic 7, 549–561.10.1111/j.1600-0854.2006.00406.xSearch in Google Scholar

Li, Z., Thiel, K., Thul, P.J., Beller, M., Kühnlein, R.P., and Welte, M.A. (2012). Lipid droplets control the maternal histone supply of Drosophila embryos. Curr. Biol. 22, 2104–2113.10.1016/j.cub.2012.09.018Search in Google Scholar

Manning, B.D., Tee, A.R., Logsdon, M.N., Blenis, J., and Cantley, L.C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151–162.10.1016/S1097-2765(02)00568-3Search in Google Scholar

McHugh, B., Krause, S.A., Yu, B., Deans, A.M., Heasman, S., McLaughlin, P., and Heck, M.M. (2004). Invadolysin: a novel, conserved metalloprotease links mitotic structural rearrangements with cell migration. J. Cell Biol. 167, 673–686.10.1083/jcb.200405155Search in Google Scholar PubMed PubMed Central

Miura, S., Gan, J.W., Brzostowski, J., Parisi, M.J., Schultz, C.J., Londos, C., Oliver, B., and Kimmel, A.R. (2002). Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, Drosophila, and Dictyostelium. J. Biol. Chem. 277, 32253–32257.10.1074/jbc.M204410200Search in Google Scholar PubMed

Müller, G., Over, S., Wied, S., and Frick, W. (2008). Association of (c)AMP-degrading glycosylphosphatidylinositol-anchored proteins with lipid droplets is induced by palmitate, H2O2 and the sulfonylurea drug, glimepiride, in rat adipocytes. Biochemistry 47, 1274–1287.10.1021/bi7022915Search in Google Scholar PubMed

Munafó, D.B. and Colombo, M.I. (2001). A novel assay to study autophagy: regulation of autophagosome vacuole size by amino acid deprivation. J. Cell Sci. 114, 3619–3629.10.1242/jcs.114.20.3619Search in Google Scholar PubMed

Musselman, L.P., Fink, J.L., Narzinski, K., Ramachandran, P.V., Hathiramani, S.S., Cagan, R.L., and Baranski, T.J. (2011). A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis. Models Mech. 4, 842–849.10.1242/jcs.102947Search in Google Scholar

Naslavsky, N., Rahajeng, J., Rapaport, D., Horowitz, M., and Caplan, S. (2007). EHD1 regulates cholesterol homeostasis and lipid droplet storage. Biochem. Biophys. Res. Commun. 357, 792–799.10.1016/j.bbrc.2007.04.022Search in Google Scholar PubMed PubMed Central

Norman, B.H., Shih, C., Toth, J.E., Ray, J.E., Dodge, J.A., Johnson, D.W., Rutherford, P.G., Schultz, R.M., Worzalla, J.F., and Vlahos, C.J. (1996). Studies on the mechanism of phosphatidylinositol 3-kinase inhibition by wortmannin and related analogs. J. Med. Chem. 39, 1106–1111.10.1021/jm950619pSearch in Google Scholar PubMed

Oshiro, N., Yoshino, K., Hidayat, S., Tokunaga, C., Hara, K., Eguchi, S., Avruch, J., and Yonezawa, K. (2004). Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes. Cells 9, 359–366.10.1111/j.1356-9597.2004.00727.xSearch in Google Scholar PubMed

Ozeki, S., Cheng, J., Tauchi-Sato, K., Hatano, N., Taniguchi, H., and Fujimoto, T. (2005). Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci. 118, 2601–2611.10.1242/jcs.02401Search in Google Scholar PubMed

Potter, C.J., Pedraza, L.G., and Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658–665.10.1038/ncb840Search in Google Scholar PubMed

Prusty, D., Park, B.H., Davis, K.E., and Farmer, S.R. (2002). Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARg) and C/EBPa gene expression during the differentiation of 3T3-L1 preadipocytes. J. Biol. Chem. 277, 46226–46232.10.1074/jbc.M207776200Search in Google Scholar PubMed

Rao, S.G., Janiszewski, M.M., Duca, E., Nelson, B., Abhinav, K., Panagakou, I., Vass, S., and Heck, M.M. (2015). Invadolysin acts genetically via the SAGA complex to modulate chromosome structure. Nucleic Acids Res. 43, 3546–3562.10.1093/nar/gkv211Search in Google Scholar PubMed PubMed Central

Rawlings, N.D. and Barrett, A.J. (1999). MEROPS: the peptidase database. Nucleic Acids Res. 27, 325–331.10.1093/nar/27.1.325Search in Google Scholar PubMed PubMed Central

Rosen, E.D. and MacDougald, O.A. (2006). Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885–896.10.1038/nrm2066Search in Google Scholar PubMed

Rosen, E.D. and Spiegelman, B.M. (2000). Peroxisome proliferator-activated receptor g ligands and atherosclerosis: ending the heartache. J. Clin. Invest. 106, 629–631.10.1172/JCI10909Search in Google Scholar PubMed PubMed Central

Rosen, E.D., Sarraf, P., Troy, A.E., Bradwin, G., Moore, K., Milstone, D.S., Spiegelman, B.M., and Mortensen, R.M. (1999). PPARg is required for the differentiation of adipose tissue in vivo and in vitro. Mol. Cell 4, 611–617.10.1016/S1097-2765(00)80211-7Search in Google Scholar

Sakaue, H., Ogawa, W., Matsumoto, M., Kuroda, S., Takata, M., Sugimoto, T., Spiegelman, B.M., and Kasuga, M. (1998). Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J. Biol. Chem. 273, 28945–28952.10.1074/jbc.273.44.28945Search in Google Scholar

Scherzer, C.R., Jensen, R.V., Gullans, S.R., and Feany, M.B. (2003). Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson’s disease. Hum. Mol. Genet. 12, 2457–2466.10.1093/hmg/ddg265Search in Google Scholar

Smirnova, E., Goldberg, E.B., Makarova, K.S., Lin, L., Brown, W.J., and Jackson, C.L. (2006). ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells. EMBO Rep. 7, 106–113.10.1038/sj.embor.7400559Search in Google Scholar

Student, A.K., Hsu, R.Y., and Lane, M.D. (1980). Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. J. Biol. Chem. 255, 4745–4750.10.1016/S0021-9258(19)85559-XSearch in Google Scholar

Taniguchi, C.M., Emanuelli, B., and Kahn, C.R. (2006). Critical nodes in signalling pathways: insights into insulin action. Nat. Rev. Mol. Cell Biol. 7, 85–96.10.1038/nrm1837Search in Google Scholar

Teixeira, L., Rabouille, C., Rørth, P., Ephrussi, A., and Vanzo, N.F. (2003). Drosophila Perilipin/ADRP homologue Lsd2 regulates lipid metabolism. Mech. Dev. 120, 1071–1081.10.1016/S0925-4773(03)00158-8Search in Google Scholar

Teleman, A.A., Chen, Y.W., and Cohen, S.M. (2005). 4E-BP functions as a metabolic brake used under stress conditions but not during normal growth. Genes. Dev. 19, 1844–1848.10.1101/gad.341505Search in Google Scholar

Tontonoz, P., Hu, E., and Spiegelman, B.M. (1994). Stimulation of adipogenesis in fibroblasts by PPARg 2, a lipid-activated transcription factor. Cell 79, 1147–1156.10.1016/0092-8674(94)90006-XSearch in Google Scholar

Tseng, Y.H., Kriauciunas, K.M., Kokkotou, E., and Kahn, C.R. (2004). Differential roles of insulin receptor substrates in brown adipocyte differentiation. Mol. Cell Biol. 24, 1918–1929.10.1128/MCB.24.5.1918-1929.2004Search in Google Scholar PubMed PubMed Central

Tsukiyama-Kohara, K., Poulin, F., Kohara, M., DeMaria, C.T., Cheng, A., Wu, Z., Gingras, A.C., Katsume, A., Elchebly, M., Spiegelman, B.M., et al. (2001). Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nat. Med. 7, 1128–1132.10.1038/nm1001-1128Search in Google Scholar

Turro, S., Ingelmo-Torres, M., Estanyol, J.M., Tebar, F., Fernandez, 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, 1254–1269.10.1111/j.1600-0854.2006.00465.xSearch in Google Scholar

Um, S.H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P.R., Kozma, S.C., Auwerx, J., et al. (2004). Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431, 200–205.10.1038/nature02866Search in Google Scholar

Vass, S. and Heck, M.M. (2013). Perturbation of invadolysin disrupts cell migration in zebrafish (Danio rerio). Exp. Cell Res. 319, 1198–1212.10.1016/j.yexcr.2013.02.005Search in Google Scholar

Vereshchagina, N. and Wilson, C. (2006). Cytoplasmic activated protein kinase Akt regulates lipid-droplet accumulation in Drosophila nurse cells. Development 133, 4731–4735.10.1242/dev.02659Search in Google Scholar

Vlahos, C.J., Matter, W.F., Hui, K.Y., and Brown, R.F. (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269, 5241–5248.10.1016/S0021-9258(17)37680-9Search in Google Scholar

Wabitsch, M., Brenner, R.E., Melzner, I., Braun, M., Möller, P., Heinze, E., Debatin, K.M., and Hauner, H. (2001). Characterization of a human preadipocyte cell strain with high capacity for adipose differentiation. Int. J. Obes. Relat. Metab. Disord. 25, 8–15.10.1038/sj.ijo.0801520Search in Google Scholar PubMed

Walther, T.C. and Farese, R.V. (2012). Lipid droplets and cellular lipid metabolism. Annu. Rev. Biochem. 81, 687–714.10.1146/annurev-biochem-061009-102430Search in Google Scholar PubMed PubMed Central

Wang, Z., Wilson, W.A., Fujino, M.A., and Roach, P.J. (2001). Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol. Cell Biol. 21, 5742–5752.10.1128/MCB.21.17.5742-5752.2001Search in Google Scholar PubMed PubMed Central

Welte, M.A. (2015). Expanding roles for lipid droplets. Curr. Biol. 25, R470–R481.10.1016/j.cub.2015.04.004Search in Google Scholar PubMed PubMed Central

Wolins, 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. (2006). OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization. Diabetes 55, 3418–3428.10.2337/db06-0399Search in Google Scholar PubMed

Wong, R.H. and Sul, H.S. (2010). Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective. Curr. Opin. Pharmacol. 10, 684–691.10.1016/j.coph.2010.08.004Search in Google Scholar PubMed PubMed Central

Xuan, J.Y., Hughes-Benzie, R.M., and MacKenzie, A.E. (1999). A small interstitial deletion in the GPC3 gene causes Simpson-Golabi-Behmel syndrome in a Dutch-Canadian family. J. Med. Genet. 36, 57–58.10.1136/jmg.36.1.57Search in Google Scholar

Xue, Y., Ren, J., Gao, X., Jin, C., Wen, L., and Yao, X. (2008). GPS 2.0, a tool to predict kinase-specific phosphorylation sites in hierarchy. Mol. Cell Proteomics 7, 1598–1608.10.1074/mcp.M700574-MCP200Search in Google Scholar PubMed PubMed Central

Yamaguchi, T., Omatsu, N., Matsushita, S., and Osumi, T. (2004). CGI-58 interacts with perilipin and is localized to lipid droplets. Possible involvement of CGI-58 mislocalization in Chanarin-Dorfman syndrome. J. Biol. Chem. 279, 30490–30497.10.1074/jbc.M403920200Search in Google Scholar PubMed

Yamakawa, T., Whitson, R.H., Li, S.L., and Itakura, K. (2008). Modulator recognition factor-2 is required for adipogenesis in mouse embryo fibroblasts and 3T3-L1 cells. Mol. Endocrinol. 22, 441–453.10.1210/me.2007-0271Search in Google Scholar PubMed PubMed Central

Yang, Q., Inoki, K., Kim, E., and Guan, K.L. (2006). TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc. Natl. Acad. Sci. USA 103, 6811–6816.10.1073/pnas.0602282103Search in Google Scholar PubMed PubMed Central

Yu, W., Chen, Z., Zhang, J., Zhang, L., Ke, H., Huang, L., Peng, Y., Zhang, X., Li, S., Lahn, B.T., et al. (2008). Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells. Mol. Cell Biochem. 310, 11–18.10.1007/s11010-007-9661-9Search in Google Scholar PubMed

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, 1852–1860.10.1242/jcs.012013Search in Google Scholar PubMed PubMed Central

Zhou, Y., Wang, D., Li, F., Shi, J., and Song, J. (2006). Different roles of protein kinase C-bI and -d in the regulation of adipocyte differentiation. Int J Biochem Cell Biol. 38, 2151–2163.10.1016/j.biocel.2006.06.009Search in Google Scholar PubMed

Zimmermann, R., Strauss, J.G., Haemmerle, G., Schoiswohl, G., Birner-Gruenberger, R., Riederer, M., Lass, A., Neuberger, G., Eisenhaber, F., Hermetter, A., et al. (2004). Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306, 1383–1386.10.1126/science.1100747Search in Google Scholar PubMed

Zirin, J., Nieuwenhuis, J., and Perrimon, N. (2013). Role of autophagy in glycogen breakdown and its relevance to chloroquine myopathy. PLoS Biol. 11, e1001708.10.1371/journal.pbio.1001708Search in Google Scholar PubMed PubMed Central


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Received: 2016-6-8
Accepted: 2016-9-4
Published Online: 2016-9-13
Published in Print: 2017-3-1

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