Insight into insulin secretion from transcriptome and genetic analysis of insulin-producing cells of Drosophila

Genetics

Volumn 197, Issue 1, 2014, Pages 175-192

  Cao, Jian ^a,b   Ni, Julie ^a,c   Ma, Wenxiu ^a   Shi, Vanessa ^a   Milla, Luis A ^a   Park, Sangbin ^a   Spletter, Maria L ^a   Tang, Sheng ^a   Zhang, Jun ^a   Wei, Xing ^a   Kim, Seung K ^a   Scott, Matthew P ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b RUTGERS UNIVERSITY   (United States)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DROSOPHILA PROTEIN; INSULIN; INSULIN LIKE PEPTIDE; INSULIN LIKE PEPTIDE 2; KINESIN; MESSENGER RNA; PEPTIDE; RAB PROTEIN; RAB1 PROTEIN; TRANSCRIPTOME; UNC 104 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTHROPOD LARVA; ARTICLE; CELL FUNCTION; CELL PROLIFERATION; CONTROLLED STUDY; DROSOPHILA; EMBRYO; GENE EXPRESSION; GENE SILENCING; GENOME ANALYSIS; GOLGI COMPLEX; IMMUNOFLUORESCENCE; INSECT CELL; INSULIN METABOLISM; INSULIN PRODUCING CELL; INSULIN RELEASE; LASER MICRODISSECTION; MALE; METABOLIC REGULATION; NERVE FIBER; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SECRETION; PROTEIN TRANSPORT; RNA SEQUENCE; SIGNAL TRANSDUCTION; ANIMAL; CARBOHYDRATE METABOLISM; CYTOLOGY; DROSOPHILA MELANOGASTER; GENE EXPRESSION PROFILING; GENETICS; GROWTH, DEVELOPMENT AND AGING; HEMOLYMPH; LARVA; METABOLISM; NUCLEOTIDE SEQUENCE; SECRETION (PROCESS);

ANIMALS; AXONS; CARBOHYDRATE METABOLISM; CONSERVED SEQUENCE; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; GENE EXPRESSION PROFILING; HEMOLYMPH; INSULIN; INSULIN-SECRETING CELLS; LARVA; MALE; RNA, MESSENGER;

EID: 84901359710     PISSN: 00166731     EISSN: 19432631     Source Type: Journal    
DOI: 10.1534/genetics.113.160663     Document Type: Article

References (109)

1. Adams, M. D., S. E. Celniker, R. A. Holt, C. A. Evans, J. D. Gocayne et al., 2000 The genome sequence of Drosophila melanogaster. Science 287: 2185-2195.
2. Adeghate, E., and A. S. Ponery, 2002 GABA in the endocrine pancreas: cellular localization and function in normal and diabetic rats. Tissue Cell 34: 1-6.
3. Ai, J., J. Duan, X. Lv, M. Chen, Q. Yang et al., 2010 Overexpression of FoxO1 causes proliferation of cultured pancreatic beta cells exposed to low nutrition. Biochemistry 49: 218-225.
4. Arntfield, M. E., and D. van der Kooy, 2011 b-Cell evolution: how the pancreas borrowed from the brain: the shared toolbox of genes expressed by neural and pancreatic endocrine cells may reflect their evolutionary relationship. Bioessays 33: 582-587.
5. Atouf, F., P. Czernichow, and R. Scharfmann, 1997 Expression of neuronal traits in pancreatic beta cells. Implication of neuronrestrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer. J. Biol. Chem. 272: 1929-1934.
6. Bader, R., L. Sarraf-Zadeh, M. Peters, N. Moderau, H. Stocker et al., 2013 The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain. J. Cell Sci. 126: 2571-2576.
7. Bai, H., P. Kang, and M. Tatar, 2012 Drosophila insulin-like peptide-6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin-like peptide-2 from the brain. Aging Cell 11: 978-985.
8. Baker, K. D., and C. S. Thummel, 2007 Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila. Cell Metab. 6: 257-266.
9. Barkus, R. V., O. Klyachko, D. Horiuchi, B. J. Dickson, and W. M. Saxton, 2008 Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides. Mol. Biol. Cell 19: 274-283.
10. Baugh, L. R., A. A. Hill, E. L. Brown, and C. P. Hunter, 2001 Quantitative analysis of mRNA amplification by in vitro transcription. Nucleic Acids Res. 29: E29.
11. Bohni, R., J. Riesgo-Escovar, S. Oldham, W. Brogiolo, H. Stocker et al., 1999 Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97: 865-875.
12. Brogiolo, W., H. Stocker, T. Ikeya, F. Rintelen, R. Fernandez et al., 2001 An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11: 213-221.
13. Brunner, Y., Y. Coute, M. Iezzi, M. Foti, M. Fukuda et al., 2007 Proteomics analysis of insulin secretory granules. Mol. Cell. Proteomics 6: 1007-1017.
14. Chan, C. C., S. Scoggin, D. Wang, S. Cherry, T. Dembo et al., 2011 Systematic discovery of Rab GTPases with synaptic functions in Drosophila. Curr. Biol. 21: 1704-1715.
15. Chell, J. M., and A. H. Brand, 2010 Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell 143: 1161-1173.
16. Chintapalli, V. R., J. Wang, and J. A. Dow, 2007 Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat. Genet. 39: 715-720.
17. Colombani, J., S. Raisin, S. Pantalacci, T. Radimerski, J. Montagne et al., 2003 A nutrient sensor mechanism controls Drosophila growth. Cell 114: 739-749.
18. Cooper, A. A., A. D. Gitler, A. Cashikar, C. M. Haynes, K. J. Hill et al., 2006 Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313: 324-328.
19. Cui, J., Z. Wang, Q. Cheng, R. Lin, X. M. Zhang et al., 2011 Targeted inactivation of kinesin-1 in pancreatic betacells in vivo leads to insulin secretory deficiency. Diabetes 60: 320-330.
20. Davidson, H. W., C. J. Rhodes, and J. C. Hutton, 1988 Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic beta cell via two distinct site-specific endopeptidases. Nature 333: 93-96.
21. Davidson, J. K., S. Falkmer, B. K. Mehrotra, and S. Wilson, 1971 Insulin assays and light microscopical studies of digestive organs in protostomian and deuterostomian species and in coelenterates. Gen. Comp. Endocrinol. 17: 388-401.
22. Dean, P. M., 1973 Ultrastructural morphometry of the pancreatic b-cell. Diabetologia 9: 115-119.
23. de Velasco, B., T. Erclik, D. Shy, J. Sclafani, H. Lipshitz et al., 2007 Specification and development of the pars intercerebralis and pars lateralis, neuroendocrine command centers in the Drosophila brain. Dev. Biol. 302: 309-323.
24. Dietzl, G., D. Chen, F. Schnorrer, K. C. Su, Y. Barinova et al., 2007 A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448: 151-156.
25. Donelan, M. J., G. Morfini, R. Julyan, S. Sommers, L. Hays et al., 2002 Ca2+-dependent dephosphorylation of kinesin heavy chain on beta-granules in pancreatic beta-cells. Implications for regulated beta-granule transport and insulin exocytosis. J. Biol. Chem. 277: 24232-24242.
26. Dong, H., M. Kumar, Y. Zhang, A. Gyulkhandanyan, Y. Y. Xiang et al., 2006 Gamma-aminobutyric acid up-and downregulates insulin secretion from beta cells in concert with changes in glucose concentration. Diabetologia 49: 697-705.
27. Escurat, M., K. Djabali, C. Huc, F. Landon, C. Becourt et al., 1991 Origin of the beta cells of the islets of Langerhans is further questioned by the expression of neuronal intermediate filament proteins, peripherin and NF-L, in the rat insulinoma RIN5F cell line. Dev. Neurosci. 13: 424-432.
28. Fujita, P. A., B. Rhead, A. S. Zweig, A. S. Hinrichs, D. Karolchik et al., 2011 The UCSC Genome Browser database: update 2011. Nucleic Acids Res. 39: D876-D882.
29. Geminard, C., E. J. Rulifson, and P. Leopold, 2009 Remote control of insulin secretion by fat cells in Drosophila. Cell Metab. 10: 199-207.
30. German, M. S., 1993 Glucose sensing in pancreatic islet beta cells: the key role of glucokinase and the glycolytic intermediates. Proc. Natl. Acad. Sci. USA 90: 1781-1785.
31. Glassmeier, G., M. Hopfner, E. O. Riecken, B. Mann, H. Buhr et al., 1998 Inhibition of L-type calcium channels by somatostatins in human neuroendocrine tumor cells of the gut. Ann. N. Y. Acad. Sci. 859: 208-209.
32. Goodwin, P. R., J. M. Sasaki, and P. Juo, 2012 Cyclin-dependent kinase 5 regulates the polarized trafficking of neuropeptide-containing dense-core vesicles in Caenorhabditis elegans motor neurons. J. Neurosci. 32: 8158-8172.
33. Gronke, S., D. F. Clarke, S. Broughton, T. D. Andrews, and L. Partridge, 2010 Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet. 6: e1000857.
34. Harashima, S., A. Clark, M. R. Christie, and A. L. Notkins, 2005 The dense core transmembrane vesicle protein IA-2 is a regulator of vesicle number and insulin secretion. Proc. Natl. Acad. Sci. USA 102: 8704-8709.
35. Haselton, A. T., and Y. W. Fridell, 2010 Adult Drosophila melanogaster as a model for the study of glucose homeostasis. Aging (Albany, NY) 2: 523-526.
36. Hickey, A. J., J. W. Bradley, G. L. Skea, M. J. Middleditch, C. M. Buchanan et al., 2009 Proteins associated with immunopurified granules from a model pancreatic islet beta-cell system: proteomic snapshot of an endocrine secretory granule. J. Proteome Res. 8: 178-186.
37. Hoy, M., P. O. Berggren, and J. Gromada, 2003 Involvement of protein kinase C-epsilon in inositol hexakisphosphate-induced exocytosis in mouse pancreatic beta-cells. J. Biol. Chem. 278: 35168-35171.
38. Huang da, W., B. T. Sherman, and R. A. Lempicki, 2009a Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37: 1-13.
39. Huang da, W., B. T. Sherman, and R. A. Lempicki, 2009b Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4: 44-57.
40. Hwang, H. J., and E. Rulifson, 2011 Serial specification of diverse neuroblast identities from a neurogenic placode by Notch and Egfr signaling. Development 138: 2883-2893.
41. Hwangbo, D. S., B. Gershman, M. P. Tu, M. Palmer, and M. Tatar, 2004 Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429: 562-566.
42. Ikeya, T., M. Galic, P. Belawat, K. Nairz, and E. Hafen, 2002 Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Curr. Biol. 12: 1293-1300.
43. Iser, W. B., M. S. Gami, and C. A. Wolkow, 2007 Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs. Dev. Biol. 303: 434-447.
44. Iyer, E. P., and D. N. Cox, 2010 Laser capture microdissection of Drosophila peripheral neurons. J. Vis. Exp.
45. Iyer, E. P., S. C. Iyer, M. J. Sulkowski, and D. N. Cox, 2009 Isolation and purification of Drosophila peripheral neurons by magnetic bead sorting. J. Vis. Exp., No. 34: pii: 1599.
46. Jensen, J., 2004 Gene regulatory factors in pancreatic development. Dev. Dyn. 229: 176-200.
47. Karolchik, D., R. Baertsch, M. Diekhans, T. S. Furey, A. Hinrichs et al., 2003 The UCSC Genome Browser Database. Nucleic Acids Res. 31: 51-54.
48. Kasai, H., H. Hatakeyama, M. Ohno, and N. Takahashi, 2010 Exocytosis in islet beta-cells. Adv. Exp. Med. Biol. 654: 305-338.
49. Kasai, K., M. Ohara-Imaizumi, N. Takahashi, S. Mizutani, S. Zhao et al., 2005 Rab27a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation. J. Clin. Invest. 115: 388-396.
50. Kern, J. V., Y. V. Zhang, S. Kramer, J. E. Brenman, and T. M. Rasse, 2013 The kinesin-3, unc-104 regulates dendrite morphogenesis and synaptic development in Drosophila. Genetics 195: 59-72.
51. Kieffer, T. J., R. S. Heller, C. A. Leech, G. G. Holz, and J. F. Habener, 1997 Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells. Diabetes 46: 1087-1093.
52. Kim, J., H. Bang, S. Ko, I. Jung, H. Hong et al., 2008 Drosophila ia2 modulates secretion of insulin-like peptide. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 151: 180-184.
53. Kim, S. K., and E. J. Rulifson, 2004 Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells. Nature 431: 316-320.
54. Kimura, T., and I. Niki, 2011 Rab27a in pancreatic beta-cells, a busy protein in membrane trafficking. Prog. Biophys. Mol. Biol. 107: 219-223.
55. Kimura, T., Y. Kaneko, S. Yamada, H. Ishihara, T. Senda et al., 2008 The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines. J. Cell Sci. 121: 3092-3098.
56. Ku, G. M., H. Kim, I. W. Vaughn, M. J. Hangauer, C. M. Oh et al., 2012 Research resource: RNA-Seq reveals unique features of the pancreatic b-cell transcriptome. Mol. Endocrinol. 26: 1783-1792.
57. Lam, T. K., R. Gutierrez-Juarez, A. Pocai, and L. Rossetti, 2005 Regulation of blood glucose by hypothalamic pyruvate metabolism. Science 309: 943-947.
58. Lang, J. E., M. J. Magbanua, J. H. Scott, G. M. Makrigiorgos, G. Wang et al., 2009 A comparison of RNA amplification techniques at sub-nanogram input concentration. BMC Genomics 10: 326.
59. Li, W., S. G. Kennedy, and G. Ruvkun, 2003 daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Genes Dev. 17: 844-858.
60. Lilly, B., B. Zhao, G. Ranganayakulu, B. M. Paterson, R. A. Schulz et al., 1995 Requirement of MADS domain transcription factor D-MEF2 for muscle formation in Drosophila. Science 267: 688-693.
61. Lo, K. Y., A. Kuzmin, S. M. Unger, J. D. Petersen, and M. A. Silverman, 2011 KIF1A is the primary anterograde motor protein required for the axonal transport of dense-core vesicles in cultured hippocampal neurons. Neurosci. Lett. 491: 168-173.
62. Mendez, C. F., I. B. Leibiger, B. Leibiger, M. Hoy, J. Gromada et al., 2003 Rapid association of protein kinase C-epsilon with insulin granules is essential for insulin exocytosis. J. Biol. Chem. 278: 44753-44757.
63. Meng, Y. X., G. W. Wilson, M. C. Avery, C. H. Varden, and R. Balczon, 1997 Suppression of the expression of a pancreatic beta-cell form of the kinesin heavy chain by antisense oligonucleotides inhibits insulin secretion from primary cultures of mouse beta-cells. Endocrinology 138: 1979-1987.
64. Miguel-Aliaga, I., S. Thor, and A. P. Gould, 2008 Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons. PLoS Biol. 6: e58.
65. Miller, M. R., K. J. Robinson, M. D. Cleary, and C. Q. Doe, 2009 TU-tagging: cell type-specific RNA isolation from intact complex tissues. Nat. Methods 6: 439-441.
66. Nassel, D. R., 2012 Insulin-producing cells and their regulation in physiology and behavior of Drosophila. Can. J. Zool. 90: 476-488.
67. Newsholme, P., C. Gaudel, and N. H. McClenaghan, 2010 Nutrient regulation of insulin secretion and beta-cell functional integrity. Adv. Exp. Med. Biol. 654: 91-114.
68. Ni, J. Q., M. Markstein, R. Binari, B. Pfeiffer, L. P. Liu et al., 2008 Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nat. Methods 5: 49-51.
69. O'Brien, L. E., S. S. Soliman, X. Li, and D. Bilder, 2011 Altered modes of stem cell division drive adaptive intestinal growth. Cell 147: 603-614.
70. Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, and N. Hirokawa, 1995 The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 81: 769-780.
71. Okamoto, N., N. Yamanaka, Y. Yagi, Y. Nishida, H. Kataoka et al., 2009 A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila. Dev. Cell 17: 885-891.
72. Pack-Chung, E., P. T. Kurshan, D. K. Dickman, and T. L. Schwarz, 2007 A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nat. Neurosci. 10: 980-989.
73. Park, D., J. A. Veenstra, J. H. Park, and P. H. Taghert, 2008 Mapping peptidergic cells in Drosophila: where DIMM fits in. PLoS ONE 3: e1896.
74. Philipson, L. H., A. Kusnetsov, T. Larson, Y. Zeng, and G. Westermark, 1993 Human, rodent, and canine pancreatic beta-cells express a sodium channel alpha 1-subunit related to a fetal brain isoform. Diabetes 42: 1372-1377.
75. Puig, O., M. T. Marr, M. L. Ruhf, and R. Tjian, 2003 Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. Genes Dev. 17: 2006-2020.
76. Rajan, A., and N. Perrimon, 2012 Drosophila cytokine unpaired 2 regulates physiological homeostasis by remotely controlling insulin secretion. Cell 151: 123-137.
77. Rao, S., C. Lang, E. S. Levitan, and D. L. Deitcher, 2001 Visualization of neuropeptide expression, transport, and exocytosis in Drosophila melanogaster. J. Neurobiol. 49: 159-172.
78. Rayburn, L. Y., J. Rhea, S. R. Jocoy, and M. Bender, 2009 The proprotein convertase amontillado (amon) is required during Drosophila pupal development. Dev. Biol. 333: 48-56.
79. Rolls, M. M., 2011 Neuronal polarity in Drosophila: sorting out axons and dendrites. Dev. Neurobiol. 71: 419-429.
80. Rorsman, P., and E. Renstrom, 2003 Insulin granule dynamics in pancreatic beta cells. Diabetologia 46: 1029-1045.
81. Rulifson, E. J., S. K. Kim, and R. Nusse, 2002 Ablation of insulinproducing neurons in flies: growth and diabetic phenotypes. Science 296: 1118-1120.
82. Satoh, A., F. Tokunaga, S. Kawamura, and K. Ozaki, 1997 In situ inhibition of vesicle transport and protein processing in the dominant negative Rab1 mutant of Drosophila. J. Cell Sci. 110 (Pt 23): 2943-2953.
83. Settle, S. H. Jr., M. M. Green, and K. C. Burtis, 1995 The silver gene of Drosophila melanogaster encodes multiple carboxypeptidases similar to mammalian prohormone-processing enzymes. Proc. Natl. Acad. Sci. USA 92: 9470-9474.
84. Siekhaus, D. E., and R. S. Fuller, 1999 A role for amontillado, the Drosophila homolog of the neuropeptide precursor processing protease PC2, in triggering hatching behavior. J. Neurosci. 19: 6942-6954.
85. Sivachenko, A., Y. Li, K. C. Abruzzi, and M. Rosbash, 2013 The transcription factor Mef2 links the Drosophila core clock to Fas2, neuronal morphology, and circadian behavior. Neuron 79: 281-292.
86. Slaidina, M., R. Delanoue, S. Gronke, L. Partridge, and P. Leopold, 2009 A Drosophila insulin-like peptide promotes growth during nonfeeding states. Dev. Cell 17: 874-884.
87. Sousa-Nunes, R., L. L. Yee, and A. P. Gould, 2011 Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 471: 508-512.
88. Spletter, M. L., J. Liu, H. Su, E. Giniger, T. Komiyama et al., 2007 Lola regulates Drosophila olfactory projection neuron identity and targeting specificity. Neural Dev. 2: 14.
89. Stenmark, H., 2009 Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell Biol. 10: 513-525.
90. Tabei, S. M., S. Burov, H. Y. Kim, A. Kuznetsov, T. Huynh et al., 2013 Intracellular transport of insulin granules is a subordinated random walk. Proc. Natl. Acad. Sci. USA 110: 4911-4916.
91. Takahashi, N., H. Hatakeyama, H. Okado, A. Miwa, T. Kishimoto et al., 2004 Sequential exocytosis of insulin granules is associated with redistribution of SNAP25. J. Cell Biol. 165: 255-262.
92. Tatar, M., 2004 The neuroendocrine regulation of Drosophila aging. Exp. Gerontol. 39: 1745-1750.
93. Tirouvanziam, R., C. J. Davidson, J. S. Lipsick, and L. A. Herzenberg, 2004 Fluorescence-activated cell sorting (FACS) of Drosophila hemocytes reveals important functional similarities to mammalian leukocytes. Proc. Natl. Acad. Sci. USA 101: 2912-2917.
94. Trapnell, C., L. Pachter, and S. L. Salzberg, 2009 TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105-1111.
95. Trapnell, C., B. A. Williams, G. Pertea, A. Mortazavi, G. Kwan et al., 2010 Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28: 511-515.
96. Uno, T., K. Sakamoto, Y. Isoyama, S. Hiragaki, Y. Uno et al., 2013 Relationship between the expression of Rab family GTPases and neuropeptide hormones in the brain of Bombyx mori. Histochem. Cell Biol. 139: 299-308.
97. Van Gelder, R. N., M. E. von Zastrow, A. Yool, W. C. Dement, J. D. Barchas et al., 1990 Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc. Natl. Acad. Sci. USA 87: 1663-1667.
98. Wang, E., 2005 RNA amplification for successful gene profiling analysis. J. Transl. Med. 3: 28.
99. Wang, E., L.D. Miller, G. A. Ohnmacht, E. T. Liu, and F. M. Marincola, 2000 High-fidelity mRNA amplification for gene profiling. Nat. Biotechnol. 18: 457-459.
100. Wang, H., R. Ishizaki, J. Xu, K. Kasai, E. Kobayashi et al., 2013 The Rab27a effector exophilin7 promotes fusion of secretory granules that have not been docked to the plasma membrane. Mol. Biol. Cell 24: 319-330.
101. Wang, M. C., D. Bohmann, and H. Jasper, 2005 JNK extends life span and limits growth by antagonizing cellular and organismwide responses to insulin signaling. Cell 121: 115-125.
102. Wang, S., N. Tulina, D. L. Carlin, and E. J. Rulifson, 2007 The origin of islet-like cells in Drosophila identifies parallels to the vertebrate endocrine axis. Proc. Natl. Acad. Sci. USA 104: 19873-19878.
103. Xu, E., M. Kumar, Y. Zhang, W. Ju, T. Obata et al., 2006 Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system. Cell Metab. 3: 47-58.
104. Ye, B., Y. Zhang, W. Song, S. H. Younger, L. Y. Jan et al., 2007 Growing dendrites and axons differ in their reliance on the secretory pathway. Cell 130: 717-729.
105. Yi, Z., H. Yokota, S. Torii, T. Aoki, M. Hosaka et al., 2002 The Rab27a/granuphilin complex regulates the exocytosis of insulincontaining dense-core granules. Mol. Cell. Biol. 22: 1858-1867.
106. Yonekawa, Y., A. Harada, Y. Okada, T. Funakoshi, Y. Kanai et al., 1998 Defect in synaptic vesicle precursor transport and neuronal cell death in KIF1A motor protein-deficient mice. J. Cell Biol. 141: 431-441.
107. Zahn, T. R., J. K. Angleson, M. A. MacMorris, E. Domke, J. F. Hutton et al., 2004 Dense core vesicle dynamics in Caenorhabditis elegans neurons and the role of kinesin UNC-104. Traffic 5: 544-559.
108. Zhang, H., J. Liu, C. R. Li, B. Momen, R. A. Kohanski et al., 2009 Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities. Proc. Natl. Acad. Sci. USA 106: 19617-19622.
109. Zhang, J., K. L. Schulze, P. R. Hiesinger, K. Suyama, S. Wang et al., 2007 Thirty-one flavors of Drosophila rab proteins. Genetics 176: 1307-1322.