Dataset Information

FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.

ABSTRACT: Target of Rapamycin Complex 1 (TORC1) is a master regulator that coordinates nutrient status with cell metabolism. The GTPase-activating protein towards Rags complex 1 (GATOR1) inhibits TORC1 activity and protects cells from damage during periods of stress. Here we characterize multiple pathways that regulate the expression of the GATOR1 component Nprl3 in Drosophila. We determine that the stability of Nprl3 is impacted by the Unassembled Soluble Complex Proteins Degradation (USPD) pathway. In addition, we find that FK506 binding protein 39 (FKBP39)-dependent proteolytic destruction maintains Nprl3 at low levels in nutrient replete conditions. Nutrient starvation abrogates the degradation of the Nprl3 protein and rapidly promotes Nprl3 accumulation. Consistent with a role in promoting the stability of a TORC1 inhibitor, mutations in fkbp39 decrease TORC1 activity and increase autophagy. Finally, we show that the 5'UTR of nprl3 transcripts contain a functional upstream open reading frame (uORF) that inhibits main ORF translation. In summary, our work has uncovered novel mechanisms of Nprl3 regulation and identifies an important role for FKBP39 in the control of cellular metabolism.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC8172852 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.

Zhou Ying Y Guo Jian J Wang Xinyu X Cheng Yang Y Guan Jianwen J Barman Priyam P Sun Ming-An MA Fu Yuanyuan Y Wei Wanhong W Feng Congjing C Lilly Mary A MA Wei Youheng Y

Cell death & disease 20210602 6

Target of Rapamycin Complex 1 (TORC1) is a master regulator that coordinates nutrient status with cell metabolism. The GTPase-activating protein towards Rags complex 1 (GATOR1) inhibits TORC1 activity and protects cells from damage during periods of stress. Here we characterize multiple pathways that regulate the expression of the GATOR1 component Nprl3 in Drosophila. We determine that the stability of Nprl3 is impacted by the Unassembled Soluble Complex Proteins Degradation (USPD) pathway. In a ...[more]

PMID: 34078879

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Project description:Drosophila suzukii Matsumura is an invasive species of vinegar fly that has become a prominent pest of berries and other soft-skinned fruits. Unlike most other Drosophila species, female D. suzukii flies lay their eggs in ripening and ripe fruits and larvae develop within the fruit. To understand how D. suzukii larvae utilize ripe and ripening fruits, which usually have low levels of protein, we investigated the microbiota of field-captured and laboratory-reared D. suzukii flies and further examined the combined influence of diet and microbes on host fitness. Field-captured flies were associated with diverse microbiota, which varied significantly with sampling location and season. In contrast, laboratory-reared flies possessed strikingly lower bacterial abundance and diversity. A comparison of conventionally reared (CR) and germ-free (GF) flies revealed that the microbiota of D. suzukii does not alter its development significantly but decreases its life span under conditions of a nutrient-sufficient diet. However, the microbiota is essential for D. suzukii development on strawberry-based or blueberry-based fruit diets. This developmental failure could be rescued by reassociation with single bacterial or fungal species or by the addition of a high quantity of heat-killed microbes. In addition, we found that proteins are limiting with respect to fly development on fruit-based diets and that GF flies show signs of protein starvation. Taken together, our study results demonstrate that the microbiota provides key proteins required for the development of D. suzukii reared on fresh fruit. Our work shows that the impact of microbes on fly fitness depends strongly on nutritional conditions.IMPORTANCE Animals are commonly associated with specific microbes, which play important roles in host development and fitness. However, little information about the function of microbes has been available for the important invasive pest Drosophila suzukii, also known as Spotted wing drosophila. Our study results demonstrate that the abundance and structure of microbiota in D. suzukii are strongly affected by the environment, where microbes have variable roles depending on the nutritional situation. For instance, we found that the presence of microbes is deleterious for flies growing on a protein-rich diet and yet is beneficial for flies growing on a diet of protein-poor fruits. Additionally, germ-free flies must feed on microbes to obtain the necessary protein for larval development on strawberries and blueberries. Our report validates the complexity seen in host-microbe interactions and may provide information useful for D. suzukii pest control.

Dataset Information

FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.

Publications

FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila.

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