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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 398, Issue 3

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A role for the metalloprotease invadolysin in insulin signaling and adipogenesis

Ching-Wen Chang
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
  • Other articles by this author:
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/ Kanishk Abhinav
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
  • Other articles by this author:
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/ Francesca Di Cara
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
  • Other articles by this author:
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/ Ioanna Panagakou
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
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/ Sharron Vass
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
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/ Margarete M.S. Heck
  • Corresponding author
  • University of Edinburgh, Queen’s Medical Research Institute, University/BHF Center for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
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Published Online: 2016-09-13 | DOI: https://doi.org/10.1515/hsz-2016-0226

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.

This article offers supplementary material which is provided at the end of the article.

Keywords: adipogenesis; insulin signaling; lipid droplets; metalloprotease

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.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.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.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.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.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.CrossrefGoogle 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.CrossrefGoogle Scholar

  • Blom, N., Gammeltoft, S., and Brunak, S. (1999). Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol. 294, 1351–1362.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • Chikte, S., Panchal, N., and Warnes, G. (2014). Use of LysoTracker dyes: a flow cytometric study of autophagy. Cytometry A 85, 169–178.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • Farmer, S.R. (2006). Transcriptional control of adipocyte formation. Cell Metab. 4, 263–273.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • Garofalo, R.S. (2002). Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol. Metab. 13, 156–162.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.CrossrefGoogle Scholar

  • Gomis-Ruth, F.X. (2003). Structural aspects of the metzincin clan of metalloendopeptidases. Mol. Biotechnol. 24, 157–202.CrossrefGoogle Scholar

  • Green, H. and Kehinde, O. (1976). Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells. Cell 7, 105–113.CrossrefGoogle 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.CrossrefGoogle Scholar

  • Holm, C. (2003). Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem. Soc. Trans. 31, 1120–1124.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle 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.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.Google Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.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.Google Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • Potter, C.J., Pedraza, L.G., and Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658–665.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • Rawlings, N.D. and Barrett, A.J. (1999). MEROPS: the peptidase database. Nucleic Acids Res. 27, 325–331.CrossrefGoogle Scholar

  • Rosen, E.D. and MacDougald, O.A. (2006). Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885–896.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle 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.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.CrossrefGoogle 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle 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.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.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.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.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.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.CrossrefGoogle Scholar

  • Walther, T.C. and Farese, R.V. (2012). Lipid droplets and cellular lipid metabolism. Annu. Rev. Biochem. 81, 687–714.Google Scholar

  • 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.CrossrefGoogle Scholar

  • Welte, M.A. (2015). Expanding roles for lipid droplets. Curr. Biol. 25, R470–R481.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.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.Google Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • 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.CrossrefGoogle Scholar

  • 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.CrossrefGoogle Scholar

  • 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.Google Scholar

  • Zirin, J., Nieuwenhuis, J., and Perrimon, N. (2013). Role of autophagy in glycogen breakdown and its relevance to chloroquine myopathy. PLoS Biol. 11, e1001708.CrossrefGoogle Scholar

About the article

aChing-Wen Chang and Kanishk Abhinav: These authors contributed equally to this work.

bPresent address: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.

cPresent address: Department of Cell Biology, Faculty of Medicine, University of Alberta, Edmonton T6G 2H7, Canada.

dPresent address: Edinburgh Napier University, Sighthill Court, Edinburgh EH11 4BN, UK.


Received: 2016-06-08

Accepted: 2016-09-04

Published Online: 2016-09-13

Published in Print: 2017-03-01


Citation Information: Biological Chemistry, Volume 398, Issue 3, Pages 373–393, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2016-0226.

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