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PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus

Xu, Daqian, Wang, Zheng, Zhang, Yuxue, Jiang, Wei, Pan, Yi, Song, Bao-Liang, Chen, Yan·2015·Nature Communications
DOI 10.1038/ncomms9100PMC PMC4560833
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Abstract

Cholesterol biosynthesis is regulated by transcription factors SREBPs and their escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is unknown. Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the Golgi. PAQR3 promotes Scap/SREBP complex formation, potentiates SREBP processing and enhances lipid synthesis. The mutually exclusive interaction between Scap and PAQR3 or Insig-1 is regulated by cholesterol level. PAQR3 knockdown in liver blunts SREBP pathway and decreases hepatic cholesterol content. Disrupting the interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP processing and activation. Thus, PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis.

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Metadata

Authors
Xu, D., Wang, Z., Zhang, Y., Jiang, W., Pan, Y., Song, B.-L., & Chen, Y.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2015-08-27
Volume
6
Issue
1
ISSN
2041-1723
DOI
10.1038/ncomms9100
PMC
PMC4560833
Cited by
89
References
2
Language
en
Licence

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