RGD Reference Report - Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. - Rat Genome Database

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Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins.

Authors: Hammad, SM  Barth, JL  Knaak, C  Argraves, WS 
Citation: Hammad SM, etal., J Biol Chem. 2000 Apr 21;275(16):12003-8.
RGD ID: 1641845
Pubmed: (View Article at PubMed) PMID:10766831

Cubilin has recently been shown to function as an endocytic receptor for high density lipoproteins (HDL). The lack of apparent transmembrane and cytoplasmic domains in cubilin raises questions as to the means by which it can mediate endocytosis. Since cubilin has been reported to bind the endocytic receptor megalin, we explored the possibility that megalin acts in conjunction with cubilin to mediate HDL endocytosis. While megalin did not bind to HDL, delipidated HDL, or apoA-I, it was found to copurify with cubilin isolated by HDL-Sepharose affinity chromatography. Cubilin and megalin exhibited coincident patterns of mRNA expression in mouse tissues including the kidney, ileum, thymus, placenta, and yolk sac endoderm. The expression of both receptors in yolk sac endoderm-like cells was inducible by retinoic acid treatment but not by conditions of sterol depletion. Suppression of megalin activity or expression by treatment with either megalin antibodies or megalin antisense oligodeoxynucleotides resulted in inhibition of cubilin-mediated endocytosis of HDL. Furthermore, megalin antisense oligodeoxynucleotide treatment resulted in reduced cell surface expression of cubilin. These data demonstrate that megalin acts together with cubilin to mediate HDL endocytosis and further suggest that megalin may play a role in the intracellular trafficking of cubilin.


Gene Ontology Annotations    

Biological Process

Cellular Component
cell surface  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Lrp2  (LDL receptor related protein 2)

Additional Information