Dataset Information


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

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.


PROVIDER: S-EPMC4560833 | BioStudies | 2015-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2005-01-01 | S-EPMC552931 | BioStudies
1000-01-01 | S-EPMC1851665 | BioStudies
2016-01-01 | S-EPMC4959871 | BioStudies
1000-01-01 | S-EPMC3093874 | BioStudies
2003-01-01 | S-EPMC196858 | BioStudies
2019-01-01 | S-EPMC6463267 | BioStudies
1000-01-01 | S-EPMC1851663 | BioStudies
2002-01-01 | S-EPMC129331 | BioStudies
2015-01-01 | S-EPMC4643405 | BioStudies
2017-01-01 | S-EPMC5656429 | BioStudies