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XB-ART-56427
J Cell Sci 2018 May 23;13110:. doi: 10.1242/jcs.212522.
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The VLDL receptor regulates membrane progesterone receptor trafficking and non-genomic signaling.

Nader N , Dib M , Courjaret R , Hodeify R , Machaca R , Graumann J , Machaca K .


Abstract
Progesterone mediates its physiological functions through activation of both transcription-coupled nuclear receptors and seven-pass-transmembrane progesterone receptors (mPRs), which transduce the rapid non-genomic actions of progesterone by coupling to various signaling modules. However, the immediate mechanisms of action downstream of mPRs remain in question. Herein, we use an untargeted quantitative proteomics approach to identify mPR interactors to better define progesterone non-genomic signaling. Surprisingly, we identify the very-low-density lipoprotein receptor (VLDLR) as an mPRβ (PAQR8) partner that is required for mPRβ plasma membrane localization. Knocking down VLDLR abolishes non-genomic progesterone signaling, which is rescued by overexpressing VLDLR. Mechanistically, we show that VLDLR is required for mPR trafficking from the endoplasmic reticulum to the Golgi. Taken together, our data define a novel function for the VLDLR as a trafficking chaperone required for the mPR subcellular localization and, as such, non-genomic progesterone-dependent signaling.This article has an associated First Person interview with the first author of the paper.

PubMed ID: 29685893
Article link: J Cell Sci


Species referenced: Xenopus
Genes referenced: cdk1 mapk1 paqr8 pgrmc1 vldlr
GO keywords: oocyte maturation [+]
Morpholinos: vldlr MO1 vldlr cMO1


Article Images: [+] show captions