Document Detail


The structure and function of Niemann-Pick C1-like 1 protein.
MedLine Citation:
PMID:  18460917     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Intestinal absorption and biliary excretion of cholesterol represent two major pathways by which the body regulates cholesterol homeostasis. Niemann-Pick C1-like 1 (NPC1L1) is a polytopic transmembrane protein containing a sterol-sensing domain of unknown function. In 2004, NPC1L1 was identified to be essential for intestinal cholesterol absorption, a process that is sensitive to a cholesterol absorption inhibitor ezetimibe. This review summarizes recent studies on NPC1L1 function and proposes a model for NPC1L1-dependent cholesterol uptake. RECENT FINDINGS: Cell culture experiments have shown that NPC1L1 mediates cellular uptake of various sterols but seems to have lower affinity to plant sterols than cholesterol. Transgenic animal studies have demonstrated that hepatic NPC1L1 has the potential to regulate biliary cholesterol excretion. Cholesterol and many transcriptional factors appear to regulate NPC1L1 gene expression. NPC1L1 protein is enriched in the apical membrane of polarized cells and its intracellular itineraries are clearly regulated by cholesterol availability. Evidence suggests cholesterol-regulated clathrin-mediated endocytosis is likely the cellular basis for NPC1L1-dependent cholesterol uptake, which may reconcile disagreement regarding NPC1L1 subcellular localization. SUMMARY: NPC1L1 may have evolved at two sites (apical membrane of enterocytes and canalicular membrane of hepatocytes) to mediate cholesterol uptake through a clathrin-mediated endocytic process, protecting the body against fecal and biliary loss of cholesterol.
Authors:
Liqing Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in lipidology     Volume:  19     ISSN:  0957-9672     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-07     Completed Date:  2008-08-05     Revised Date:  2008-08-18    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  England    
Other Details:
Languages:  eng     Pagination:  263-9     Citation Subset:  IM    
Affiliation:
Department of Pathology Section on Lipid Sciences, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1040, USA. lyu@wfubmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Biliary Tract / secretion
Cholesterol / secretion
Gene Expression Regulation
Humans
Intestinal Absorption
Liver / metabolism
Membrane Proteins / chemistry*,  genetics,  physiology*
Membrane Transport Proteins / chemistry*,  genetics,  physiology*
Protein Conformation
Structure-Activity Relationship
Subcellular Fractions / metabolism
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Membrane Transport Proteins; 0/NPC1L1 protein, human; 0/Npc1l1 protein, mouse; 57-88-5/Cholesterol
Comments/Corrections
Erratum In:
Curr Opin Lipidol. 2008 Aug;19(4):440

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