title: Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila.
abstract: Developing animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors.
authors.affiliation: Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: Louise Y
authors.initials: LY
authors.lastname: Cheng
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bailey
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Leevers
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ragan
authors.forename: Paul C
authors.initials: PC
authors.lastname: Driscoll
authors.forename: Alex P
authors.initials: AP
authors.lastname: Gould
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism*; D005508:Food Deprivation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011123:Polyploidy; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases