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Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

Official URL:https://doi.org/10.1016/j.cmet.2010.08.006
PubMed:View item in PubMed
Creators Name:Kjolby, M. and Andersen, O.M. and Breiderhoff, T. and Fjorback, A.W. and Pedersen, K.M. and Madsen, P. and Jansen, P. and Heeren, J. and Willnow, T.E. and Nykjaer, A.
Journal Title:Cell Metabolism
Journal Abbreviation:Cell Metab
Volume:12
Number:3
Page Range:213-223
Date:8 September 2010
Keywords:Humdisease, Proteins, Animals, Mice
Abstract:Recent genome-wide association studies (GWAS) have revealed strong association of hypercholesterolemia and myocardial infarction with SNPs on human chromosome 1p13.3. This locus covers three genes: SORT1, CELSR2, and PSRC1. We demonstrate that sortilin, encoded by SORT1, is an intracellular sorting receptor for apolipoprotein (apo) B100. It interacts with apoB100 in the Golgi and facilitates the formation and hepatic export of apoB100-containing lipoproteins, thereby regulating plasma low-density lipoprotein (LDL) cholesterol. Absence of sortilin in gene-targeted mice reduces secretion of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3.
ISSN:1550-4131
Publisher:Cell Press (U.S.A.)
Item Type:Article

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