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Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status. In Drosophila, insulin-producing median neurosecretory cells (IPCs) regulate larval growth by secreting insulin-like peptides (dILPs) in a diet-dependent manner. Previous studies have shown that nutrition affects dILP secretion through humoral signals derived from the fat body. Here we uncover a novel mechanism that operates cell autonomously in the IPCs to regulate dILP secretion. We observed that impairment of ribosome biogenesis specifically in the IPCs strongly inhibits dILP secretion, which consequently leads to reduced body size and a delay in larval development. This response is dependent on p53, a known surveillance factor for ribosome biogenesis. A downstream effector of this growth inhibitory response is an atypical MAP kinase ERK7 (ERK8/MAPK15), which is upregulated in the IPCs following impaired ribosome biogenesis as well as starvation. We show that ERK7 is sufficient and essential to inhibit dILP secretion upon impaired ribosome biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation. Thus, we conclude that a cell autonomous ribosome surveillance response, which leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth under limiting dietary conditions.
ORGANISMAL GROWTH, BIOGENESIS, FAT-CELLS, QH426-470, PATHWAY, NUTRITIONAL CONTROL, Insulin-Secreting Cells, Genetics, Animals, Drosophila Proteins, Insulin, Biochemistry, cell and molecular biology, Mitogen-Activated Protein Kinase Kinases, CYTOPLASMIC MATURATION, TOR, DEPENDENT REGULATION, Drosophila melanogaster, Genetics, developmental biology, physiology, Larva, KINASE-ACTIVITY, Intercellular Signaling Peptides and Proteins, CELL-GROWTH, Tumor Suppressor Protein p53, Ribosomes, Research Article, Signal Transduction
ORGANISMAL GROWTH, BIOGENESIS, FAT-CELLS, QH426-470, PATHWAY, NUTRITIONAL CONTROL, Insulin-Secreting Cells, Genetics, Animals, Drosophila Proteins, Insulin, Biochemistry, cell and molecular biology, Mitogen-Activated Protein Kinase Kinases, CYTOPLASMIC MATURATION, TOR, DEPENDENT REGULATION, Drosophila melanogaster, Genetics, developmental biology, physiology, Larva, KINASE-ACTIVITY, Intercellular Signaling Peptides and Proteins, CELL-GROWTH, Tumor Suppressor Protein p53, Ribosomes, Research Article, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 25 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |