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

Abstract:

: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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

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

doi

10.1371/journal.pbio.3000901

subject

Has Abstract

pub_date

2020-11-02 00:00:00

pages

e3000901

issue

11

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-19-03653

journal_volume

18

pub_type

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