The VLDL receptor regulates membrane progesterone receptor trafficking and non-genomic signaling

Research output: Contribution to journalArticle

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, nongenomic progesterone-dependent signaling. This article has an associated First Person interview with the first author of the paper.

Original languageEnglish
Article numberjcs212522
JournalJournal of Cell Science
Volume131
Issue number10
DOIs
Publication statusPublished - 15 May 2018

Fingerprint

Progesterone Receptors
Progesterone
Membranes
Cytoplasmic and Nuclear Receptors
Endoplasmic Reticulum
Proteomics
Transcriptional Activation
Cell Membrane
VLDL receptor
Interviews

Keywords

  • Endoplasmic reticulum
  • Golgi
  • Meiotic arrest
  • Membrane progesterone receptor
  • Oocyte
  • Oocyte maturation
  • Progesterone
  • Trafficking
  • VLDLR

ASJC Scopus subject areas

  • Cell Biology

Cite this

The VLDL receptor regulates membrane progesterone receptor trafficking and non-genomic signaling. / Nader, Nancy; Dib, Maya; Courjaret, Raphael Jean; Hodeify, Rawad; Machaca, Raya; Graumann, Johannes; Machaca, Khaled.

In: Journal of Cell Science, Vol. 131, No. 10, jcs212522, 15.05.2018.

Research output: Contribution to journalArticle

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AU - Dib, Maya

AU - Courjaret, Raphael Jean

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AU - Machaca, Raya

AU - Graumann, Johannes

AU - Machaca, Khaled

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