Article

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

Pontifical Catholic University of Chile, CiudadSantiago, Santiago Metropolitan, Chile
Journal of Biological Chemistry (Impact Factor: 4.6). 09/2006; 281(39):28975-80. DOI: 10.1074/jbc.M603802200
Source: PubMed

ABSTRACT 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.

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    • "SR-BI contains two cytosolic regions, one of approximately 10 amino acids at its N-terminus and the other of ∼40 amino acids at its C-terminus [4]. The terminal 3-4 amino acids of the C-terminal cytosolic domain represents a binding site for an adaptor protein called PDZK1 which plays an important role in protecting SR-BI protein from degradation in hepatocytes [21] [22] [23]. The precise sequences that direct SR-BI towards degradation in the absence of PDZK1 binding remain to be identified; however it is presumed that they reside in the C-terminal cytosolic tail of SR-BI. "
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    Cholesterol 01/2011; 2011(2090-1283):687939. DOI:10.1155/2011/687939
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    • "PDZK1 is another member of the NHERF family that also binds to NHE3 (Gisler et al. 2003b), and it was therefore suggested to call it NHERF3. It is a multifunctional PDZ-domain protein with high expression levels in kidney, where it is involved in the scaffolding and regulation of a variety of membrane transporters (Gisler et al. 2003a,b; Thomson et al. 2005b; Kato et al. 2006), the liver, where it regulates the membrane abundance of the scavenger receptor (Kocher et al. 2003b; Yesilaltay et al. 2006) and in the intestine. We had previously studied electroneutral sodium absorption in the small intestine of pdzk1+/+ and −/− mice, and found a significantly reduced basal Na + absorptive rate "
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