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TIP Revista Especializada en Ciencias Químico-Biológicas

2016, Número 2

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TIP Rev Esp Cienc Quim Biol 2016; 19 (2)


Crecimiento y Metabolismo: La regulación y la vía de la Insulina desde la Mosca de la Fruta, Drosophila melanogaster

Otero-Moreno D, Peña-Rangel MT, Riesgo-Escovar JR

Idioma: Español
Referencias bibliográficas: 77
Paginas: 116-126
Archivo PDF: 752.98 Kb.


RESUMEN

Drosophila melanogaster, la mosca de la fruta, es un organismo genético modelo que en años recientes se ha usado exitosamente para estudiar el control del metabolismo y el crecimiento. A pesar de poseer algunas diferencias con las vías de señalización homólogas a las de los vertebrados, las semejanzas son profundas y claras. En D. melanogaster, la vía de la insulina, homóloga a la de los vertebrados, regula tanto el metabolismo como el crecimiento del organismo a través de un receptor membranal único. A su vez, esta vía –que conjunta lo que en vertebrados es la vía de la insulina y la de los péptidos parecidos a la insulina- está regulada por la ingesta de nutrientes (carbohidratos y proteínas) y por el control hormonal (hormona del crecimiento, ecdisona, upd2, hormona adipocinética, Ilp8). En consecuencia, normalmente se obtiene un crecimiento adaptable a las condiciones nutricionales que influye, como en los vertebrados, en el promedio de vida y en la capacidad reproductiva con un tamaño típico y una diferenciación armónica, a tono con el bauplan del organismo. Por el contrario las mutaciones y desviaciones dan por resultado partes desproporcionadas, menor capacidad reproductiva, y disminución tanto del tamaño como de la proliferación, y hasta la muerte.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Owusu-Ansah, E. & Perrimon, N. Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases. Dis. Model Mech. 7, 343-350, doi:10.1242/dmm.012989 (2014).

  2. Smith, W. W., Thomas, J., Liu, J., Li, T. & Moran, T. H. From fat fruit fly to human obesity. Physiol. Behav. 136, 15-21, doi:10.1016/j.physbeh.2014.01.017 (2014).

  3. Rubin, G. M. Drosophila melanogaster as an experimental organism. Science 240, 1453-1459 (1988).

  4. Teleman, A. A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem. J. 425, 13-26, doi:10.1042/ BJ20091181 (2010).

  5. Rajan, A. & Perrimon, N. Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell 151, 123-137, doi:10.1016/j.cell.2012.08.019 (2012).

  6. Vallejo, C. G., Juárez-Carreño, S., Bolívar, J., Morante, J. & Domínguez, M. A brain circuit that synchronizes growth and maduration revealed through Dilp8 binding to Lgr3. Science 350, doi:10.1126/science.aac676 (2015).

  7. Colombani, J. et al. Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability. Curr. Biol. 25, 2723-2729, doi:10.1016/j.cub.2015.09.020 (2015).

  8. Colombani, J., Andersen, D. S. & Leopold, P. Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336, 582-585, doi:10.1126/science.1216689 (2012).

  9. Garelli, A., Gontijo, A. M., Miguela, V., Caparros, E. & Domínguez, M. Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579-582, doi:10.1126/science.1216735 (2012).

  10. Pool, A. H. & Scott, K. Feeding regulation in Drosophila. Curr. Opin. Neurobiol. 29, 57-63, doi:10.1016/j.conb.2014.05.008 (2014).

  11. Kim, J. & Neufeld, T. P. Dietary sugar promotes systemic TOR activation in Drosophila through AKH-dependent selective secretion of Dilp3. Nat. Commun. 6, 6846, doi:10.1038/ncomms7846 (2015).

  12. Koyama, T., Mendes, C. C. & Mirth, C. K. Mechanisms regulating nutrition-dependent developmental plasticity through organspecific effects in insects. Front Physiol. 4, 263, doi:10.3389/fphys.2013.00263 (2013).

  13. Kamakura, M. Royalactin induces queen differentiation in honeybees. Nature 473, 478-483, doi:10.1038/nature10093 (2011).

  14. Andersen, D. S., Colombani, J. & Leopold, P. Drosophila growth and development: keeping things in proportion. Cell Cycle 11, 2971-2972, doi:10.4161/cc.21466 (2012).

  15. Sheldon, A. L., Zhang, J., Fei, H. & Levitan, I. B. SLOB, a SLOWPOKE channel binding protein, regulates insulin pathway signaling and metabolism in Drosophila. PLoS One 6, e23343, doi:10.1371/journal.pone.0023343 (2011).

  16. Fridell, Y. W. et al. Increased uncoupling protein (UCP) activity in Drosophila insulin-producing neurons attenuates insulin signaling and extends lifespan. Aging (Albany NY) 1, 699-713 (2009).

  17. Kreneisz, O., Chen, X., Fridell, Y. W. & Mulkey, D. K. Glucose increases activity and Ca2+ in insulin-producing cells of adult Drosophila. Neuroreport 21, 1116-1120, doi:10.1097/ WNR.0b013e3283409200 (2010).

  18. Nassel, D. R., Kubrak, O. I., Liu, Y., Luo, J. & Lushchak, O. V. Factors that regulate insulin producing cells and their output in Drosophila. Front Physiol. 4, 252, doi:10.3389/fphys.2013.00252 (2013).

  19. The FlyBase database of the Drosophila genome projects and community literature. Nucleic Acids Res. 31, 172-175 (2003).

  20. Colombani, J. et al. A nutrient sensor mechanism controls Drosophila growth. Cell 114, 739-749 (2003).

  21. Kwak, S. J. et al. Drosophila adiponectin receptor in insulin producing cells regulates glucose and lipid metabolism by controlling insulin secretion. PLoS One 8, e68641, doi:10.1371/journal.pone.0068641 (2013).

  22. Pool, A. H. et al. Four GABAergic interneurons impose feeding restraint in Drosophila. Neuron 83, 164-177, doi:10.1016/j. neuron.2014.05.006 (2014).

  23. Okamoto, H. & Nishimura, E. K. Signaling from Glia and Cholinergic Neurons Controls Nutrient-Dependent Production of an Insulin-like Peptide for Drosophila Body Growth. Dev. Cell 35, 295-310 (2015).

  24. Rulifson, E. J., Kim, S. K. & Nusse, R. Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296, 1118-1120, doi:10.1126/science.1070058 (2002).

  25. R, N. D. & J, V. B. Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and postrelease action of the insulin-like peptides. Cell. Mol. Life Sci., doi:10.1007/s00018-015-2063-3 (2015).

  26. Palu, R. A. S. & Thummel, C. S. Linking Nutrients to Growth through a Positive Feedback Loop. Dev. Cell 35, 265-266, doi:http://dx.doi.org/10.1016/j.devcel.2015.10.026 (2015).

  27. Brogiolo, W. et al. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11, 213-221 (2001).

  28. Broughton, S. J. et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proceedings of the National Academy of Sciences of the United States of America 102, 3105-3110, doi:10.1073/pnas.0405775102 (2005).

  29. Alic, N., Hoddinott, M. P., Vinti, G. & Partridge, L. Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor. Aging Cell 10, 137-147, doi:10.1111/j.1474-9726.2010.00653.x (2011).

  30. Arquier, N. et al. Drosophila ALS regulates growth and metabolism through functional interaction with insulin-like peptides. Cell Metab. 7, 333-338, doi:10.1016/j.cmet.2008.02.003 (2008).

  31. Okamoto, N. et al. A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes Dev. 27, 87-97, doi:10.1101/gad.204479.112 (2013).

  32. Lee, K. S. et al. Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat. Cell Biol. 10, 468-475, doi:10.1038/ncb1710 (2008).

  33. Kapan, N., Lushchak, O. V., Luo, J. & Nassel, D. R. Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin. Cell Mol. Life Sci. 69, 4051-4066, doi:10.1007/s00018-012-1097-z (2012).

  34. Kaplan, D. D., Zimmermann, G., Suyama, K., Meyer, T. & Scott, M. P. A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size. Genes Dev. 22, 1877-1893, doi:10.1101/gad.1670508 (2008).

  35. Luo, J., Becnel, J., Nichols, C. D. & Nassel, D. R. Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor. Cell Mol. Life Sci. 69, 471-484, doi:10.1007/s00018-011-0789-0 (2012).

  36. Birse, R. T., Soderberg, J. A., Luo, J., Winther, A. M. & Nassel, D. R. Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR. The Journal of experimental biology 214, 4201-4208, doi:10.1242/jeb.062091 (2011).

  37. Miyamoto, T., Wright, G. & Amrein, H. Nutrient sensors. Curr. Biol. 23, R369-373, doi:10.1016/j.cub.2013.04.002 (2013).

  38. Miyamoto, T. & Amrein, H. Diverse roles for the Drosophila fructose sensor Gr43a. Fly (Austin) 8, 19-25, doi:10.4161/ fly.27241 (2014).

  39. Nassel, D. R. & Broeck, J. V. Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides. Cell Mol. Life Sci., doi:10.1007/s00018-015-2063-3 (2015).

  40. Lushchak, O. V., Carlsson, M. A. & Nassel, D. R. Food odors trigger an endocrine response that affects food ingestion and metabolism. Cell Mol. Life Sci. 72, 3143-3155, doi:10.1007/s00018-015-1884-4 (2015).

  41. Fernández, R., Tabarini, D., Azpiazu, N., Frasch, M. & Schlessinger, J. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. Embo. J. 14, 3373-3384 (1995).

  42. Bohni, R. et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865-875 (1999).

  43. Slack, C. et al. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS Genet. 6, e1000881, doi:10.1371/journal.pgen.1000881 (2010).

  44. Werz, C., Kohler, K., Hafen, E. & Stocker, H. The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 5, e1000596, doi:10.1371/journal.pgen.1000596 (2009).

  45. Almudi, I., Poernbacher, I., Hafen, E. & Stocker, H. The Lnk/ SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell Commun. Signal 11, 26, doi:10.1186/1478-811X-11-26 (2013).

  46. Leevers, S. J., Weinkove, D., MacDougall, L. K., Hafen, E. & Waterfield, M. D. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. Embo. J. 15, 6584-6594 (1996).

  47. Alessi, D. R. et al. 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. Curr. Biol. 7, 776-789 (1997).

  48. Verdu, J., Buratovich, M. A., Wilder, E. L. & Birnbaum, M. J. Cellautonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat. Cell Biol. 1, 500-506, doi:10.1038/70293 (1999).

  49. Huang, H. et al. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126, 5365-5372 (1999).

  50. Papadopoulou, D., Bianchi, M. W. & Bourouis, M. Functional studies of shaggy/glycogen synthase kinase 3 phosphorylation sites in Drosophila melanogaster melanogaster. Mol. Cell Biol. 24, 4909-4919, doi:10.1128/MCB.24.11.4909-4919.2004 (2004).

  51. Junger, M. A. et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2, 20, doi:10.1186/1475- 4924-2-20 (2003).

  52. Kramer, J. M., Slade, J. D. & Staveley, B. E. foxo is required for resistance to amino acid starvation in Drosophila. Genome 51, 668-672, doi:10.1139/G08-047 (2008).

  53. Kramer, J. M., Davidge, J. T., Lockyer, J. M. & Staveley, B. E. Expression of Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev. Biol. 3, 5, doi:10.1186/1471-213X-3-5 (2003).

  54. Potter, C. J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357-368 (2001).

  55. Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E. & Hariharan, I. K. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345-355 (2001).

  56. Ito, N. & Rubin, G. M. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96, 529-539 (1999).

  57. Zhang, Y. et al. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5, 578-581, doi:10.1038/ncb999 (2003).

  58. Saucedo, L. J. et al. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5, 566- 571, doi:10.1038/ncb996 (2003).

  59. Potter, C. J., Pedraza, L. G. & Xu, T. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658-665, doi:10.1038/ncb840 (2002).

  60. Wang, B. et al. A hormone-dependent module regulating energy balance. Cell 145, 596-606, doi:10.1016/j.cell.2011.04.013 (2011).

  61. Oldham, S. & Hafen, E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 13, 79-85 (2003).

  62. Seto, B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin. Transl. Med. 1, 29, doi:10.1186/2001-1326-1-29 (2012).

  63. Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P. & Guan, K. L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10, 935-945, doi:10.1038/ncb1753 (2008).

  64. Chantranupong, L., Wolfson, R. L. & Sabatini, D. M. Nutrientsensing mechanisms across evolution. Cell 161, 67-83, doi:10.1016/j.cell.2015.02.041 (2015).

  65. Li, L. et al. Regulation of mTORC1 by the Rab and Arf GTPases. J. Biol. Chem. 285, 19705-19709, doi:10.1074/jbc.C110.102483 (2010).

  66. Miron, M., Lasko, P. & Sonenberg, N. Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol. Cell Biol. 23, 9117-9126 (2003).

  67. Stewart, M. J., Berry, C. O., Zilberman, F., Thomas, G. & Kozma, S. C. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Proceedings of the National Academy of Sciences of the United States of America 93, 10791-10796 (1996).

  68. Montagne, J. et al. Drosophila S6 kinase: a regulator of cell size. Science 285, 2126-2129 (1999).

  69. Hernández, G. & Sierra, J. M. Translation initiation factor eIF-4E from Drosophila: cDNA sequence and expression of the gene. Biochimica et biophysica acta 1261, 427-431 (1995).

  70. Hardie, D. G. & Pan, D. A. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem. Soc. Trans. 30, 1064-1070, doi:10.1042/ (2002).

  71. Pan, D. A. & Hardie, D. G. A homologue of AMP-activated protein kinase in Drosophila melanogaster is sensitive to AMP and is activated by ATP depletion. Biochem. J. 367, 179-186, doi:10.1042/BJ20020703 (2002).

  72. Haselton, A. T. & Fridell, Y. W. Adult Drosophila melanogaster as a model for the study of glucose homeostasis. Aging (Albany NY) 2, 523-526 (2010).

  73. Baker, K. D. & Thummel, C. S. Diabetic larvae and obese fliesemerging studies of metabolism in Drosophila. Cell Metab. 6, 257-266, doi:10.1016/j.cmet.2007.09.002 (2007).

  74. Murillo-Maldonado, J. M., Sánchez-Chávez, G., Salgado, L. M., Salceda, R. & Riesgo-Escovar, J. R. Drosophila insulin pathway mutants affect visual physiology and brain function besides growth, lipid, and carbohydrate metabolism. Diabetes 60, 1632-1636, doi:10.2337/db10-1288 (2011).

  75. Murillo-Maldonado, J. M., Zeineddine, F. B., Stock, R., Thackeray, J. & Riesgo-Escovar, J. R. Insulin receptor-mediated signaling via phospholipase C-gamma regulates growth and differentiation in Drosophila. PLoS One 6, e28067, doi:10.1371/journal. pone.0028067 (2011).

  76. Haselton, A. et al. Partial ablation of adult Drosophila insulinproducing neurons modulates glucose homeostasis and extends life span without insulin resistance. Cell Cycle 9, 3063-3071, doi:10.4161/cc.9.15.12458 (2010).

  77. Casanueva, E., Kaufer-Horwitz, M., Pérez-Lizaur, A. B. & Arroyo, P. Nutriología Médica. (Editorial Médica Panamericana, 2008).




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