Deletion in Cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit

Tokuo Yamamoto, Richard W. Bishop, Michael S. Brown, Joseph L. Goldstein, David W. Russell

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)

Abstract

The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal with familial hypercholesterolemia, produces a mutant receptor for plasma low-density lipoprotein (LDL) that is not transported to the cell surface at a normal rate. Cloning and sequencing of complementary DNA's from normal and WHHL rabbits, shows that this defect arises from an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor. A similar mutation, detected by S1 nuclease mapping of LDL receptor messenger RNA, occurred in a patient with familial hypercholesterolemia whose receptor also fails to be transported to the cell surface. These findings suggest that animal cells may have foil-safe mechanisms that prevent the surface expression of improperly folded proteins with unpaired or improperly bonded cysteine residues.

Original languageEnglish
Pages (from-to)1230-1237
Number of pages8
JournalScience
Volume232
Issue number4755
DOIs
Publication statusPublished - 1986

ASJC Scopus subject areas

  • General

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