2. Academic Validation
  3. The adaptor protein GIPC1 stabilizes the scavenger receptor SR-B1 and increases its cholesterol uptake

The adaptor protein GIPC1 stabilizes the scavenger receptor SR-B1 and increases its cholesterol uptake

  • J Biol Chem. 2021 Jan-Jun:296:100616. doi: 10.1016/j.jbc.2021.100616.
Ziyu Zhang 1,  Qian Zhou 1,  Rui Liu 1,  Li Liu 2,  Wen-Jun Shen 3,  Salman Azhar 3,  Yan-Fu Qu 1,  Zhigang Guo 1,  Zhigang Hu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
  • 2 Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 3 Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California, USA; Division of Endocrinology, Gerontology and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
  • 4 Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China. Electronic address: [email protected].
PMID: 33811857 DOI: 10.1016/j.jbc.2021.100616
Abstract

The scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein (HDL) receptor, is a membrane glycoprotein that mediates selective uptake of HDL-cholesterol and Cholesterol ester (CE) into cells. SR-B1 is subject to posttranslational regulation; however, the underlying mechanisms still remain obscure. Here, we identified a novel SR-B1-interacting protein, GIPC1 (GAIP-interacting protein, C terminus 1) that interacts with SR-B1 and stabilizes SR-B1 by negative regulation of its proteasomal and lysosomal degradation pathways. The physiological interaction between SR-B1 and GIPC1 was supported by co-immunoprecipitation of wild-type and mutant GIPC1 constructs in SR-B1 ± GIPC1 overexpressing cells, in native liver cells, and in mouse liver tissues. Overexpression of GIPC1 increased endogenous SR-B1 protein levels, subsequently increasing selective HDL-cholesterol/CE uptake and cellular triglyceride (TG) and total Cholesterol (TC) levels, whereas silencing of GIPC1 in the mouse liver was associated with blunted hepatic SR-B1 levels, elevated plasma TG and TC, and attenuated hepatic TG and TC content. A positive correlation was identified between GIPC1 and SR-B1 expression, and both expressions of GIPC1 and SR-B1 from human liver samples were inversely correlated with body mass index (BMI) from human subjects. We therefore conclude that GIPC1 plays a key role in the stability and function of SR-B1 and can also effectively regulate hepatic lipid and Cholesterol metabolism. These findings expand our knowledge of the regulatory roles of GIPC1 and suggest that GIPC1 exerts a major effect on cell surface receptors such as SR-B1 and its associated hepatic lipid and Cholesterol metabolic processes.

Keywords

PDZ protein GIPC1; SR-B1; adaptor protein; cholesterol uptake; protein–protein interaction; selective lipid transport.

Figures
Products
Inhibitors & Agonists