期刊
CURRENT OPINION IN LIPIDOLOGY
卷 16, 期 2, 页码 147-152出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.mol.0000162319.54795.e5
关键词
adaptor; cholesterol; high-density lipoprotein receptor; PDZ
资金
- FIC NIH HHS [TW006153] Funding Source: Medline
- NHLBI NIH HHS [HL64737, HL52212, HL66105] Funding Source: Medline
Purpose of review A novel mechanism for the regulation of lipoprotein receptor activity is providing new insights into the control of lipid metabolism. The tissue-specific adaptors ARH (autosomal recessive hypercholesterolemia) and PDZK1 [where PDZ derives from postsynaptic density protein (PSD-95)/Drosophila discs-large (dlg)/tight-junction protein (ZO1)] have been shown to control the activities of distinct types of lipoprotein receptors in a posttranscriptional fashion, significantly affecting overall lipoprotein metabolism. This review will focus on one of these lipoprotein receptor-adaptor pairs, the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type 1) and its adaptor PDZK1. Recent findings The PDZ domain-containing adaptor protein PDZK1 has been shown to bind to and control the activity of the high-density lipoprotein receptor SR-BI via a tissue-specific posttranscriptional mechanism. Mice deficient in PDZK1 have elevated plasma cholesterol levels due to the virtually complete hepatic ablation of SR-BI, implicating PDZK1 as a novel regulator of high-density lipoprotein metabolism. Summary The functions of ARH and PDZK1 suggest that other adaptor proteins may be found to control the activities of other cell-surface receptors in a similar tissue-specific fashion. Manipulation of the expression and/or activities of such adaptors might provide new insights into receptor physiology and these adaptors may prove to be attractive targets for pharmaceutical intervention in cholesterol metabolism-related disease processes.
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