Abstract
Reproduction is a process that is extremely sensitive to changes in nutritional status. The nutritional control of oogenesis via insulin signaling has been reported; however, the mechanism underlying its sensitivity and tissue specificity has not been elucidated. Here, we determined that Drosophila Makorin RING finger protein 1 gene (Mkrn1) functions in the metabolic regulation of oogenesis. Mkrn1 was endogenously expressed at high levels in ovaries and Mkrn1 knockout resulted in female sterility. Mkrn1-null egg chambers were previtellogenic without egg production. FLP-FRT mosaic analysis revealed that Mkrn1 is essential in germline cells, but not follicle cells, for ovarian function. As well, AKT phosphorylation via insulin signaling was greatly reduced in the germline cells, but not the follicle cells, of the mutant clones in the ovaries. Furthermore, protein-rich diet elevated Mkrn1 protein levels, without increased mRNA levels. The p-AKT and p-S6K levels, downstream targets of insulin/Tor signaling, were significantly increased by a nutrient-rich diet in wild-type ovaries whereas those were low in Mkrn1exS compared to wild-type ovaries. Taken together, our results suggest that nutrient availability upregulates the Mkrn1 protein, which acts as a positive regulator of insulin signaling to confer sensitivity and tissue specificity in the ovaries for proper oogenesis based on nutritional status.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Dietary Proteins / administration & dosage
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Female
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Insulin / metabolism*
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Insulin, Regular, Human / genetics
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Insulin, Regular, Human / metabolism*
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Mutation
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Oocytes / cytology
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Oocytes / metabolism
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Oogenesis / genetics
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Ovary / cytology
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Ovary / drug effects
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Ovary / metabolism
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Signal Transduction*
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TOR Serine-Threonine Kinases / metabolism*
Substances
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Dietary Proteins
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Drosophila Proteins
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Insulin
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Insulin, Regular, Human
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Makorin ring finger protein 1
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Nerve Tissue Proteins
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Ribonucleoproteins
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target of rapamycin protein, Drosophila
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TOR Serine-Threonine Kinases
Grants and funding
This work was supported by the Korea Health Industry Development Institute (KHIDI) grant funded by the Ministry of Health & Welfare, Republic of Korea (grant No. HI16C2061) and the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT, Republic of Korea (grant No. 2012R1A5A048183) to Eun Young Kim. Eunjoo Cho was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT, Republic of Korea (grant No. 2017R1D1A1B03033549).