Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans

Joseph L. Goldstein, Sandip K. Basu, Gloria Y. Brunschede, Michael S. Brown

Research output: Contribution to journalArticlepeer-review

351 Scopus citations

Abstract

The sulfated glycosaminoglycan, heparin, was found to release 125I-labeled low density lipoprotein (125I-LDL) from its receptor site on the surface of normal human fibroblasts. Measurement of the amount of 125I-LDL released by heparin permitted the resolution of the total cellular uptake of 125I-LDL at 37°C into two components: first, an initial rapid, high affinity binding of the lipoprotein to the surface receptor, from which the 125I-LDL could be released by heparin, and second, a slower process attributable to an endocytosis of the receptor-bound lipoprotein, which rendered it resistant to heparin release. At 4°C the amount of heparin-releasable 125I-LDL was similar to that at 37°C, but interiorization of the lipoprotein did not occur at the lower temperature. The physiologic importance of the cell surface LDL receptor was emphasized by the finding that mutant fibroblasts from a subject with homozygous Familial Hypercholesterolemia, which lack the ability to take up 125I-LDL at 37°C, did not show cell surface binding of 125I-LDL, as measured by heparin release, at either 4°C or 37°C. Although heparin released 125I-LDL from its binding site, it did not release 3H-concanavalin A from its surface receptor, and conversely, α-methyl-D-mannopyranoside, which released 3H-concanavalin A, did not release surface-bound 125I-LDL. When added to the culture medium simultaneously with LDL, heparin prevented the binding of LDL to its receptor and hence prevented the LDL-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. The uptake of LDL by fibroblasts is proposed as a model of receptor-mediated adsorptive endocytosis of macromolecules in human cells.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalCell
Volume7
Issue number1
DOIs
StatePublished - Jan 1976

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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