PMID- 16867981 OWN - NLM STAT- MEDLINE DCOM- 20061127 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 281 IP - 39 DP - 2006 Sep 29 TI - PDZK1 is required for maintaining hepatic scavenger receptor, class B, type I (SR-BI) steady state levels but not its surface localization or function. PG - 28975-80 AB - PDZK1 is a multi-PDZ domain-containing adaptor protein that binds to the C terminus of the high density lipoprotein receptor, scavenger receptor, class B, type I (SR-BI), and controls the posttranscriptional, tissue-specific expression of this lipoprotein receptor. In the absence of PDZK1 (PDZK1(-/-) mice), murine hepatic SR-BI protein levels are very low (<5% of control). As a consequence, abnormal plasma lipoprotein metabolism ( approximately 1.5-1.7-fold increased total plasma cholesterol carried in both normal size and abnormally large high density lipoprotein particles) resembles, but is not as severely defective as, that in SR-BI(-/-) mice. Here we show that the total plasma cholesterol levels and size distribution of lipoproteins are virtually identical in SR-BI(-/-) and SR-BI(-/-)/PDZK1(-/-) mice, indicating that most, if not all of the effects of PDZK1 on lipoprotein metabolism are likely because of the effects of PDZK1 on SR-BI. Hepatic overexpression of wild-type SR-BI in PDZK1(-/-) mice restored near or greater than normal levels of cell surface-expressed, functional SR-BI protein levels in the livers of SR-BI(-/-)/PDZK1(-/-) mice and consequently restored apparently normal lipoprotein metabolism in the absence of PDZK1. Thus, PDZK1 is important for maintaining adequate steady state levels of SR-BI in the liver but is not essential for cell surface expression or function of hepatic SR-BI. FAU - Yesilaltay, Ayce AU - Yesilaltay A AD - Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. FAU - Kocher, Olivier AU - Kocher O FAU - Pal, Rinku AU - Pal R FAU - Leiva, Andrea AU - Leiva A FAU - Quinones, Veronica AU - Quinones V FAU - Rigotti, Attilio AU - Rigotti A FAU - Krieger, Monty AU - Krieger M LA - eng GR - HL64737/HL/NHLBI NIH HHS/United States GR - HL66105/HL/NHLBI NIH HHS/United States GR - TW006153/TW/FIC NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060725 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (CD36 Antigens) RN - 0 (Carrier Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Lipoproteins) RN - 0 (Membrane Proteins) RN - 0 (PDZK1 protein, mouse) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - CD36 Antigens/metabolism/*physiology MH - Carrier Proteins/metabolism/*physiology MH - Cell Membrane/metabolism MH - Cholesterol/blood MH - Gene Expression Regulation MH - Genotype MH - Intracellular Signaling Peptides and Proteins/chemistry/*physiology MH - Lipoproteins/metabolism MH - Membrane Proteins MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Transgenes EDAT- 2006/07/27 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/07/27 09:00 PHST- 2006/07/27 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/07/27 09:00 [entrez] AID - S0021-9258(19)33990-0 [pii] AID - 10.1074/jbc.M603802200 [doi] PST - ppublish SO - J Biol Chem. 2006 Sep 29;281(39):28975-80. doi: 10.1074/jbc.M603802200. Epub 2006 Jul 25.