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TIF-IA-Dependent Regulation of Ribosome Synthesis in Muscle Is Required to Maintain Systemic Insulin Signaling and Larval Growth


All animals need adequate nutrition to grow and develop. Studies in tissue culture and model organisms have identified the TOR kinase signaling pathway as a key nutrient-dependent regulator of growth. Under nutrient rich conditions, TOR kinase is active and stimulates metabolic processes that drive growth. Under nutrient poor conditions, TOR is inhibited and animals alter their metabolism to maintain homeostasis and survival. Here we use Drosophila larvae to identify a role for ribosome synthesis—a key metabolic process—in mediating nutrient and TOR effects on body growth. In particular, we show that ribosome synthesis specifically in larval muscle is necessary to maintain organismal growth. We find that inhibition of muscle ribosome synthesis leads to reduced systemic insulin-like growth factor signaling via two endocrine responses—decreased expression of brain derived Drosophila insulin-like peptides (dILPs) and increased expression of Imp-L2, an inhibitor of insulin signaling. As a result of these effects, body growth is reduced and larval development is delayed. These findings suggest that control of ribosome synthesis, and hence protein synthesis, in specific tissues can exert control on overall body growth.


Vyšlo v časopise: TIF-IA-Dependent Regulation of Ribosome Synthesis in Muscle Is Required to Maintain Systemic Insulin Signaling and Larval Growth. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004750
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004750

Souhrn

All animals need adequate nutrition to grow and develop. Studies in tissue culture and model organisms have identified the TOR kinase signaling pathway as a key nutrient-dependent regulator of growth. Under nutrient rich conditions, TOR kinase is active and stimulates metabolic processes that drive growth. Under nutrient poor conditions, TOR is inhibited and animals alter their metabolism to maintain homeostasis and survival. Here we use Drosophila larvae to identify a role for ribosome synthesis—a key metabolic process—in mediating nutrient and TOR effects on body growth. In particular, we show that ribosome synthesis specifically in larval muscle is necessary to maintain organismal growth. We find that inhibition of muscle ribosome synthesis leads to reduced systemic insulin-like growth factor signaling via two endocrine responses—decreased expression of brain derived Drosophila insulin-like peptides (dILPs) and increased expression of Imp-L2, an inhibitor of insulin signaling. As a result of these effects, body growth is reduced and larval development is delayed. These findings suggest that control of ribosome synthesis, and hence protein synthesis, in specific tissues can exert control on overall body growth.


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