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PLoS Biol January 1, 2020; 18 (11): e3000901.

Membrane progesterone receptor induces meiosis in Xenopus oocytes through endocytosis into signaling endosomes and interaction with APPL1 and Akt2.

Nader N , Dib M , Hodeify R , Courjaret R , Elmi A , Hammad AS , Dey R , Huang XY , Machaca K .

The steroid hormone progesterone (P4) mediates many physiological processes through either nuclear receptors that modulate gene expression or membrane P4 receptors (mPRs) that mediate nongenomic signaling. mPR signaling remains poorly understood. Here we show that the topology of mPRβ is similar to adiponectin receptors and opposite to that of G-protein-coupled receptors (GPCRs). Using Xenopus oocyte meiosis as a well-established physiological readout of nongenomic P4 signaling, we demonstrate that mPRβ signaling requires the adaptor protein APPL1 and the kinase Akt2. We further show that P4 induces clathrin-dependent endocytosis of mPRβ into signaling endosome, where mPR interacts transiently with APPL1 and Akt2 to induce meiosis. Our findings outline the early steps involved in mPR signaling and expand the spectrum of mPR signaling through the multitude of pathways involving APPL1.

PubMed ID: 33137110
PMC ID: PMC7660923
Article link: PLoS Biol

Genes referenced: abhd2 akt1 akt2 appl1 arf6 cdk1 cltc mapk1 mos myt1 paqr8 pgrmc1 plk1 prss1 ptbp1 rab5a slc20a2 snap25 tub vldlr

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References [+] :
Andersen, Protein kinase B/Akt is essential for the insulin- but not progesterone-stimulated resumption of meiosis in Xenopus oocytes. 2003, Pubmed, Xenbase