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Science 6 June 1986:
Vol. 232. no. 4755, pp. 1230 - 1237
DOI: 10.1126/science.3010466
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Articles

Science, Vol 232, Issue 4755, 1230-1237
Copyright © 1986 by American Association for the Advancement of Science

articles

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

T Yamamoto, RW Bishop, MS Brown, JL Goldstein, and DW Russell

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 fail-safe mechanisms that prevent the surface expression of improperly folded proteins with unpaired or improperly bonded cysteine residues.


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