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PDZK1 is required for maintaining hepatic scavenger receptor, class B, type I (SR-BI) steady state levels but not its

Ayce Yesilaltay1, Olivier Kocher, Rinku Pal

  • 1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

The Journal of Biological Chemistry
|July 27, 2006
PubMed

Insights

PDZK1 protein is crucial for maintaining scavenger receptor class B type I (SR-BI) levels in the liver, impacting lipoprotein metabolism. Restoring SR-BI levels normalizes cholesterol transport even without PDZK1.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • PDZK1 is an adaptor protein regulating the expression of the scavenger receptor class B type I (SR-BI).
  • Absence of PDZK1 in mice leads to significantly reduced hepatic SR-BI protein levels and altered lipoprotein metabolism.
  • SR-BI plays a critical role in high-density lipoprotein (HDL) metabolism and cholesterol transport.

Purpose of the Study:

  • To elucidate the role of PDZK1 in regulating SR-BI protein levels and its impact on lipoprotein metabolism.
  • To determine if PDZK1 is essential for SR-BI function and cell surface expression.
  • To investigate the relationship between PDZK1, SR-BI, and overall plasma cholesterol homeostasis.

Main Methods:

  • Comparative analysis of lipoprotein metabolism in wild-type, PDZK1(-/-), SR-BI(-/-), and SR-BI(-/-)/PDZK1(-/-) mice.
  • Assessment of hepatic SR-BI protein levels via Western blotting or similar techniques.
  • Functional studies involving hepatic overexpression of SR-BI in PDZK1-deficient mice.

Main Results:

  • Mice lacking both SR-BI and PDZK1 exhibited lipoprotein profiles nearly identical to those lacking only SR-BI.
  • Hepatic SR-BI protein levels were severely diminished (<5%) in PDZK1(-/-) mice, leading to dyslipidemia.
  • Overexpression of SR-BI in PDZK1(-/-) mice rescued normal lipoprotein metabolism, indicating PDZK1's role is primarily in maintaining SR-BI levels.

Conclusions:

  • PDZK1 is essential for maintaining adequate steady-state levels of SR-BI in the liver.
  • PDZK1's primary function in lipoprotein metabolism is mediated through its regulation of SR-BI protein abundance.
  • PDZK1 is not required for the cell surface expression or intrinsic function of SR-BI once it is present.

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