Related Experiment Video
Updated: Sep 30, 2026

In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
Published on: November 10, 2011
A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression
1Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. dls51@columbia.edu
Abstract:
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.
Related Concept Videos
Receptor-mediated Endocytosis
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
ER Retrieval Pathway
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
Regulation of Nuclear Protein Sorting
The Early Endosome: Endocytosis of Transferrin
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...

