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Aufnahmemechanismen und intrazelluläre Transportwege von Lipoproteinen und ihrer Komponenten in der Leber

  • S. Jäckle
  • F. Rinninger
  • U. Beisiegel
  • A. Block
  • H. Greten
  • E. Windler
Conference paper

Zusammenfassung

Drei funktionell verschiedene endosomale Franktionen wurden aus der Rattenleber isoliert und charakterisiert, um die intrazellulären Transportwege verschiedener Lipoproteine und deren Komponenten zu untersuchen. Diese endosomalen Fraktionen unterscheiden sich von anderen Zellorganellen durch hohe Konzentrationen des Annexin VI, eines Proteins, dessen Funktion bislang unbekannt war. Annexin VI, das als Markerprotein der hepatozyären Endosomen dienen kann, trägt wahrscheinlich zur Interaktion von Endosomen mit dem Zytoskelett bei.

“Low density lipoproteins” (LDL), Chylomikronen “remnants” und “high density lipoproteins” (HDL) werden zunächst in das endosomale “compartment of uncoupling of receptors and ligands” (CURL) und anschließend in die “multivesicular bodies” (MVB) aufgenommen, um schließlich lysosomal degradiert zu werden. Postprandial werden große Chylomikronen gebildet und im Nüchtern-Zustand sog. Kleine Chylomikronen. Nach intraplasmatischer Hydrolyse eines Teils der Triglyceride werden große Chylomikronen als sog. Remnants in die Leber aufgenommen. Verglichen mit kleinen Chylomikronen-Remnants, die direkt durch den LDL-Rezeptor aufgenommen werden, werden sie jedoch verzögert in die Endosomen internalisiert. Wie Leberper-fusionsexperimente mit Heparin und Heparinase zeigen, erfolgt die verzögerte Endozytose durch eine initiale Bindung großer Chylomikronen-Remnants an die hepatische Lipase. Wahrscheinlich erst nach einer weiteren Modifizierung der große Chylomikronen-Remnants an der Leberoberfläche erfolgt dann die Aufnahme durch einen Rezeptor.

Die Aufnahme von HDL-Cholesterinestern übersteigt die der HDL-Apolipoproteine. Die Cholesterinester, die selektiv, Apolipoprotein-unabhängig aufgenommen werden, akkumulieren in einer nicht-endosomalen subzellulären Fraktion, wärend intakte HDL-Partikel dem klassischen endosomal-lysosomalen Abbauweg folgen.

Summary

Three functionally distinct endosomal fractions were isolated from rat livers to investigate the intracellular trafficking of different lipoproteins and their components. These endosomal fractions are characterized by high concentrations of annexin VI, which other subcellular fractions are lacking. Annexin VI, a new marker protein of hepatocytic endosomes, may be of significance for the interaction of endosomes with the cytoskeleton.

LDL, chylomicron remnants, and HDL were taken up into the compartment of uncoupling of receptors and ligands (CURL) and are subsequently transferred to the endosomal fraction of multivesicular bodies (MVB) at the bile canalicular pole of hepatocytes. Plasma clearance and hepatic uptake of large chylomicron remnants, obtained after a fat-rich meal, occur more rapidly than that of small chylomicron remnants, which are primarily taken up by the LDL receptor. However, the internalization of large chylomicron remnants into endosomes is substantially delayed. The delay of endocytosis is probably caused by an intitial binding of large chylomicron remnants to hepatic lipase. These particles require probably further processing before they are removed by receptor mediated endocytosis.

The liver takes up cholsteryl esters of HDL at a greater fractional rate than HDL-apolipoproteins. HDL-particles are internalized by hepatocytes into CURL and MVB and are finally degraded within lysosomes. However, HDL-cholesteryl esters, taken up selectively from HDL, accumulate in a nonendosomal compartment.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • S. Jäckle
  • F. Rinninger
  • U. Beisiegel
  • A. Block
  • H. Greten
  • E. Windler

There are no affiliations available

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