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A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver.

Scavenger receptor B, type I (SR-BI) was recently shown to interact with a PDZ domain-containing protein, PDZK1 (CLAMP/Diphor-1/CAP70/NaPi-Cap1), but the importance of this interaction in vivo in terms of SR-BI function has not been determined. In an effort to elucidate the role of this interaction in vivo, the PDZK1-interacting domain of SR-BI was identified and mutated and expressed liver-specifically in mice. The PDZKI-interacting domain on SR-BI was identified as the last three carboxyl-terminal amino acids, Arg-Lys-Leu. A mutant SR-BI (SR-BIdel509) that lacked only the leucine in the PDZ-interacting domain failed to interact with PDZK1 in vitro, while showing normal selective uptake function in nonpolarized cells. Transgenic mice with liver overexpression of SR-BIdel509 showed marked accumulation of SR-BI mRNA with only a moderate increase in SR-BI protein in liver, with no reduction in plasma cholesterol levels. Measurement of cell surface SR-BI levels and HDL cholesteryl ester-selective uptake in primary hepatocytes from transgenic mice revealed that SR-BIdel509 was not expressed at the plasma membrane correlating with normal levels of selective uptake compared with hepatocytes from nontransgenic littermates. This study indicates that the PDZK1-interacting domain of SR-BI is essential for cell surface expression of SR-BI in liver and suggests that PDZK1 or other PDZ domain proteins may play an important role in regulating SR-BI cell surface expression and hence reverse cholesterol transport.

Pubmed ID: 12119305

Authors

  • Silver DL

Journal

The Journal of biological chemistry

Publication Data

September 13, 2002

Associated Grants

None

Mesh Terms

  • Animals
  • Antigens, CD36
  • Binding Sites
  • Cell Membrane
  • Cholesterol
  • Humans
  • Liver
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scavenger Receptors, Class B