Progesterone induces meiosis through two obligate co-receptors with PLA2 activity
The steroid hormone progesterone (P4) regulates multiple aspects of reproductive and metabolic physiology. Classical P4 signaling operates through nuclear receptors that regulate transcription. In addition, P4 signals through membrane P4 receptors (mPRs) in a rapid nongenomic modality. Despite the e...
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| Format: | Article |
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eLife Sciences Publications Ltd
2025-01-01
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| Online Access: | https://elifesciences.org/articles/92635 |
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| author | Nancy Nader Lama Assaf Lubna Zarif Anna Halama Sharan Yadav Maya Dib Nabeel Attarwala Qiuying Chen Karsten Suhre Steven Gross Khaled Machaca |
| author_facet | Nancy Nader Lama Assaf Lubna Zarif Anna Halama Sharan Yadav Maya Dib Nabeel Attarwala Qiuying Chen Karsten Suhre Steven Gross Khaled Machaca |
| author_sort | Nancy Nader |
| collection | DOAJ |
| description | The steroid hormone progesterone (P4) regulates multiple aspects of reproductive and metabolic physiology. Classical P4 signaling operates through nuclear receptors that regulate transcription. In addition, P4 signals through membrane P4 receptors (mPRs) in a rapid nongenomic modality. Despite the established physiological importance of P4 nongenomic signaling, the details of its signal transduction cascade remain elusive. Here, using Xenopus oocyte maturation as a well-established physiological readout of nongenomic P4 signaling, we identify the lipid hydrolase ABHD2 (α/β hydrolase domain-containing protein 2) as an essential mPRβ co-receptor to trigger meiosis. We show using functional assays coupled to unbiased and targeted cell-based lipidomics that ABHD2 possesses a phospholipase A2 (PLA2) activity that requires mPRβ. This PLA2 activity bifurcates P4 signaling by inducing clathrin-dependent endocytosis of mPRβ, resulting in the production of lipid messengers that are G-protein coupled receptor agonists. Therefore, P4 drives meiosis by inducing an ABHD2 PLA2 activity that requires both mPRβ and ABHD2 as obligate co-receptors. |
| format | Article |
| id | doaj-art-9f06b6c484234e7caab2993e2bf4060d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-9f06b6c484234e7caab2993e2bf4060d2025-01-28T15:26:34ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.92635Progesterone induces meiosis through two obligate co-receptors with PLA2 activityNancy Nader0https://orcid.org/0000-0003-1688-8174Lama Assaf1Lubna Zarif2Anna Halama3Sharan Yadav4Maya Dib5Nabeel Attarwala6Qiuying Chen7https://orcid.org/0000-0001-5909-3959Karsten Suhre8Steven Gross9Khaled Machaca10https://orcid.org/0000-0001-6215-2411Calcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, Qatar; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, United StatesCalcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, Qatar; College of Health and Life Science, Hamad bin Khalifa University, Doha, QatarCalcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, QatarDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, United States; Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, QatarCalcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, Qatar; Medical program, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, QatarCalcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, QatarDepartment of Pharmacology, Weill Cornell Medicine, New York, United States; Biological Sciences division, University of Chicago, Chicago, United StatesDepartment of Pharmacology, Weill Cornell Medicine, New York, United StatesDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, United States; Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, QatarDepartment of Pharmacology, Weill Cornell Medicine, New York, United StatesCalcium Signaling Group, Research Department, Weill Cornell Medicine Qatar, Education City, Qatar Foundation, Doha, Qatar; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, United StatesThe steroid hormone progesterone (P4) regulates multiple aspects of reproductive and metabolic physiology. Classical P4 signaling operates through nuclear receptors that regulate transcription. In addition, P4 signals through membrane P4 receptors (mPRs) in a rapid nongenomic modality. Despite the established physiological importance of P4 nongenomic signaling, the details of its signal transduction cascade remain elusive. Here, using Xenopus oocyte maturation as a well-established physiological readout of nongenomic P4 signaling, we identify the lipid hydrolase ABHD2 (α/β hydrolase domain-containing protein 2) as an essential mPRβ co-receptor to trigger meiosis. We show using functional assays coupled to unbiased and targeted cell-based lipidomics that ABHD2 possesses a phospholipase A2 (PLA2) activity that requires mPRβ. This PLA2 activity bifurcates P4 signaling by inducing clathrin-dependent endocytosis of mPRβ, resulting in the production of lipid messengers that are G-protein coupled receptor agonists. Therefore, P4 drives meiosis by inducing an ABHD2 PLA2 activity that requires both mPRβ and ABHD2 as obligate co-receptors.https://elifesciences.org/articles/92635progesteronemembrane progesterone receptor betaABHD2nongenomic signalingPLA2lipid messengers |
| spellingShingle | Nancy Nader Lama Assaf Lubna Zarif Anna Halama Sharan Yadav Maya Dib Nabeel Attarwala Qiuying Chen Karsten Suhre Steven Gross Khaled Machaca Progesterone induces meiosis through two obligate co-receptors with PLA2 activity eLife progesterone membrane progesterone receptor beta ABHD2 nongenomic signaling PLA2 lipid messengers |
| title | Progesterone induces meiosis through two obligate co-receptors with PLA2 activity |
| title_full | Progesterone induces meiosis through two obligate co-receptors with PLA2 activity |
| title_fullStr | Progesterone induces meiosis through two obligate co-receptors with PLA2 activity |
| title_full_unstemmed | Progesterone induces meiosis through two obligate co-receptors with PLA2 activity |
| title_short | Progesterone induces meiosis through two obligate co-receptors with PLA2 activity |
| title_sort | progesterone induces meiosis through two obligate co receptors with pla2 activity |
| topic | progesterone membrane progesterone receptor beta ABHD2 nongenomic signaling PLA2 lipid messengers |
| url | https://elifesciences.org/articles/92635 |
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