Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity - PubMed (original) (raw)

Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity

D M Kingsley et al. Proc Natl Acad Sci U S A. 1984 Sep.

Abstract

We have used cell fusion and mutant reversion analysis to study a collection of Chinese hamster ovary (CHO) cell mutants that are unable to bind and internalize low density lipoprotein (LDL). Pairwise cell fusions show that these LDL receptor-deficient mutants fall into three recessive complementation groups, ldlA, ldlB, and ldlC. Complementation was detected by observing the uptake of fluorescent LDL and was quantitated by measuring the degradation of 125I-labeled LDL by isolated hybrid cells. Previous studies had defined a fourth recessive complementation group, ldlD. Complementation tests between CHO cells and human fibroblasts suggested that the defects in mutants of the ldlA complementation group are analogous to those in a patient with homozygous familial hypercholesterolemia. A revertant of an ldlA mutant was isolated and appeared to be heterozygous at the ldlA locus. The phenotype of this revertant was similar to that of cells from patients with the heterozygous form of familial hypercholesterolemia. Together with recent DNA transfection studies, these results suggest that the ldlA locus is the structural gene for the LDL receptor in CHO cells. Mutants in the ldlB, ldlC, and ldlD complementation groups must have defects in genes that are required for either the regulation, synthesis, transport, recycling, or turnover of LDL receptors.

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References

    1. Somatic Cell Genet. 1976 Sep;2(5):453-67 - PubMed
    1. Anal Biochem. 1983 Dec;135(2):383-91 - PubMed
    1. Methods Enzymol. 1979;58:322-44 - PubMed
    1. J Biol Chem. 1979 Jun 25;254(12):5403-9 - PubMed
    1. Nature. 1979 Jun 21;279(5715):679-85 - PubMed

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