calderón encodes an organic cation transporter of the major facilitator superfamily required for cell growth and proliferation of Drosophila tissues

The adaptation of growth in response to dietary changes is essential for the normal development of all organisms. The insulin receptor (InR) signalling pathway controls growth and metabolism in response to nutrient availability. The elements of this pathway have been described, although little is known about the downstream elements regulated by this cascade. We identified calderón, a gene that encodes a protein with highest homology with organic cation transporters of the major facilitator superfamily, as a new transcriptional target of the InR pathway. These transporters are believed to function mainly in the uptake of sugars, as well as other organic metabolites. Genetic experiments demonstrate that calderón is required cell autonomously and downstream of the InR pathway for normal growth and proliferation of larval tissues. Our results indicate that growth of imaginal cells may be modulated by two distinct, but coordinated, nutrient-sensing mechanisms: one cell-autonomous and the other humoral.

[1]  S. Golz,et al.  Discovery of the ergothioneine transporter. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Bill Newman,et al.  Functional variants of OCTN cation transporter genes are associated with Crohn disease , 2004, Nature Genetics.

[3]  Yusuke Nakamura,et al.  An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis , 2003, Nature Genetics.

[4]  T. P. Neufeld,et al.  Body building: regulation of shape and size by PI3K/TOR signaling during development , 2003, Mechanisms of Development.

[5]  D. Goberdhan,et al.  The functions of insulin signaling: size isn't everything, even in Drosophila. , 2003, Differentiation; research in biological diversity.

[6]  R. Tjian,et al.  Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway. , 2003, Genes & development.

[7]  E. Hafen,et al.  The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling , 2003, Journal of biology.

[8]  J. Kramer,et al.  Expression of Drosophila FOXO regulates growth and can phenocopy starvation , 2003, BMC Developmental Biology.

[9]  E. Hafen,et al.  Rheb is an essential regulator of S6K in controlling cell growth in Drosophila , 2003, Nature Cell Biology.

[10]  B. Edgar,et al.  Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins , 2003, Nature Cell Biology.

[11]  E. Hafen,et al.  Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. , 2003, Molecular cell.

[12]  B. Edgar,et al.  Rheb promotes cell growth as a component of the insulin/TOR signalling network , 2003, Nature Cell Biology.

[13]  R. Nusse,et al.  Ablation of Insulin-Producing Neurons in Flies: Growth and Diabetic Phenotypes , 2002, Science.

[14]  Ginés Morata,et al.  Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development , 2002, Nature.

[15]  P. Kang,et al.  Akt/Protein Kinase B Promotes Organ Growth in Transgenic Mice , 2002, Molecular and Cellular Biology.

[16]  G. Morata,et al.  The functions of pannier during Drosophila embryogenesis. , 2001, Development.

[17]  E. Hafen,et al.  Genetic control of cell size. , 2000, Current opinion in genetics & development.

[18]  S. Leevers,et al.  Do growth and cell division rates determine cell size in multicellular organisms? , 2000, Journal of cell science.

[19]  P. Kang,et al.  The conserved phosphoinositide 3‐kinase pathway determines heart size in mice , 2000, The EMBO journal.

[20]  J. Heitman,et al.  The TOR signaling cascade regulates gene expression in response to nutrients. , 1999, Genes & development.

[21]  Michael N. Hall,et al.  The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors , 1999, Nature.

[22]  E. Hafen,et al.  Autonomous Control of Cell and Organ Size by CHICO, a Drosophila Homolog of Vertebrate IRS1–4 , 1999, Cell.

[23]  D. Emlen,et al.  The developmental basis for allometry in insects. , 1999, Development.

[24]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[25]  E. Wieschaus,et al.  The Drosophila Gene brinker Reveals a Novel Mechanism of Dpp Target Gene Regulation , 1999, Cell.

[26]  I. Conlon,et al.  Size Control in Animal Development , 1999, Cell.

[27]  M. Milán,et al.  Beadex encodes an LMO protein that regulates Apterous LIM-homeodomain activity in Drosophila wing development: a model for LMO oncogene function. , 1998, Genes & development.

[28]  A. Fraser,et al.  drICE is an essential caspase required for apoptotic activity in Drosophila cells , 1997, The EMBO journal.

[29]  E. Hafen,et al.  The Drosophila phosphoinositide 3‐kinase Dp110 promotes cell growth. , 1996, The EMBO journal.

[30]  G. Morata,et al.  Visualization of Gene Expression in Living Adult Drosophila , 1996, Science.

[31]  L H Frank,et al.  A group of genes required for maintenance of the amnioserosa tissue in Drosophila. , 1996, Development.

[32]  Gerald M. Rubin,et al.  Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death , 1995, Cell.

[33]  T. Tabata,et al.  Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis. , 1995, Development.

[34]  M. Frasch,et al.  The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. , 1995, The EMBO journal.

[35]  N. Perrimon,et al.  Dual functions of wingless in the Drosophila leg imaginal disc. , 1995, Development.

[36]  M. Akam,et al.  Dissecting the temporal requirements for homeotic gene function. , 1994, Development.

[37]  M. Frasch,et al.  tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. , 1993, Genes & development.

[38]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[39]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[40]  D. Tautz,et al.  A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback , 1989, Chromosoma.

[41]  G. Morata,et al.  Minutes: mutants of drosophila autonomously affecting cell division rate. , 1975, Developmental biology.

[42]  H. Moses,et al.  Induction of the C/EBP homologous protein (CHOP) by amino acid deprivation requires insulin-like growth factor I, phosphatidylinositol 3-kinase, and mammalian target of rapamycin signaling. , 2001, Endocrinology.

[43]  D. Le Roith,et al.  Control of growth by the somatropic axis: growth hormone and the insulin-like growth factors have related and independent roles. , 2001, Annual review of physiology.

[44]  W. Roesler,et al.  The role of C/EBP in nutrient and hormonal regulation of gene expression. , 2001, Annual review of nutrition.

[45]  A. Efstratiadis.  Genetics of mouse growth. , 1998, The International journal of developmental biology.