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

Research output: Research - peer-reviewJournal article

  • Mads Fuglsang Kjølby
  • Olav Michael Andersen
  • Tilman Breiderhoff
    Tilman BreiderhoffMax-Delbrück-Center for Molecular Medicine, 13125 Berlin, GermanyGermany
  • Anja Nawarecki Fjorback
    Anja Nawarecki FjorbackDenmark
  • Karen-Marie Pedersen
  • Peder Søndergaard Madsen
  • Pernille Jansen
    Pernille JansenDenmark
  • Jörg Heeren
    Jörg HeerenDepartment of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, HamburgGermany
  • Thomas Willnow
    Thomas WillnowMax-Delbrück-Center for Molecular Medicine, 13125 Berlin, GermanyGermany
  • Anders Nykjær
  • Department of Medical Biochemistry
  • Stereological Research Laboratory
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.
Udgivelsesdato: september 8
Original languageEnglish
JournalCell Metabolism
Issue number3
Pages (from-to)213-223
Number of pages11
StatePublished - 2010

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