Work

Dominant negative mutations of the scavenger receptor. Native receptor inactivation by expression of truncated variants.

Year: 1993

Type: article

Abstract: The bovine scavenger receptor was truncated at amino acid 266 or 310 to delete either all or part, respectively, of the collagen- like domain.The truncated receptors were inactive in the bind- ing and internalization of acetyl (Ac) low density lipoprotein (LDL).Coexpression of truncated receptor with the native re- ceptor dramatically reduced the percentage of cells internaliz- ing fluorescently labeled Ac LDL, compared with cells express- ing the native receptor alone.The mutant truncated at amino acid 266 was most effective in receptor inactivation, resulting in a 42% or 80% decrease in the percentage of cells expressing active receptor when transfected in a 1:1 or 1:2 molar ratio (native:mutant), respectively, with native receptor.Degrada- tion of 125I-Ac LDL was reduced up to 90% when the native and truncated mutant receptors were coexpressed.Scavenger re- ceptor inhibition was specific because the activity of the LDL receptor was not altered.Transient transfection of the mouse macrophage cell line P388D1 with truncated scavenger recep- tor resulted in a 65% decrease in the uptake and degradation of Ac LDL but did not decrease the degradation of j-migrating very low density lipoprotein, which is LDL receptor-mediated.These results demonstrate that expression of truncated bovine scavenger receptor inactivates both the native bovine and mu- rine scavenger receptors, producing a dominant negative pheno- type in vitro.(J.Clin.Invest.1993.92:894-902.)Key words: scavenger receptor * acetyl low density lipoprotein receptor * dominant negative mutations * acetylated low density lipoprotein * oxidized low density lipoprotein Portions ofthis work were presented at the annual meeting ofthe Amer- ican Heart Association, November 1992, and have been published as

Source: Journal of Clinical Investigation

DOI: 10.1172/jci116664

Authors: S Dejager, M Mietus-Snyder, A Friera, R E Pitas

Institution: University of California, San Francisco

Language: English

Topic: Cholesterol and Lipid Metabolism

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Tobacco-Related Disease Research Program, National Institutes of Health, University of California, San Francisco, National Heart, Lung, and Blood Institute