TY - JOUR
T1 - Posttranslational processing of the LDL receptor and its genetic disruption in familial hypercholesterolemia
AU - Tolleshaug, Helge
AU - Goldstein, Joseph L.
AU - Schneider, Wolfgang J.
AU - Brown, Michael S.
N1 - Funding Information:
James Cali, Julie Prlina and Wen-Ling Niu provided excellent technical assistance. We thank Edith Womack and Deborah Thompson for their able assistance in growing the cultured cells. This research was supported by a research grant from the National Institutes of Health. H. T. is the recipient of a fellowship from the Fogarty International Center of the National Institutes of Health.
PY - 1982/10
Y1 - 1982/10
N2 - Synthesis of the low density lipoprotein (LDL) receptor was studied by incubation of cultured human fibroblasts with 35S-methionine followed by immunoprecipitation with a monoclonal antireceptor antibody. The receptor was synthesized as a precursor with an apparent molecular weight of 120 kilodaltons (kd) that was converted to a mature form of 160 kd. This novel form of processing occurred 15-30 min after synthesis and did not appear to be due to the simple addition of N-linked oligosaccharide chains. Fibroblasts from a child with the phenotype of homozygous familial hypercholesterolemia showed a disruption in receptor processing. This child has two different mutant alleles at the LDL receptor locus. One allele, inherited from his heterozygous mother, produces an abnormal 120 kd protein that cannot be processed to the mature 160 kd form. The other allele, inherited from his heterozygous father, produces a receptor that is synthesized as an elongated 170 kd precursor which undergoes a 40 kd increase in molecular weight to form an abnormally large receptor of 210 kd.
AB - Synthesis of the low density lipoprotein (LDL) receptor was studied by incubation of cultured human fibroblasts with 35S-methionine followed by immunoprecipitation with a monoclonal antireceptor antibody. The receptor was synthesized as a precursor with an apparent molecular weight of 120 kilodaltons (kd) that was converted to a mature form of 160 kd. This novel form of processing occurred 15-30 min after synthesis and did not appear to be due to the simple addition of N-linked oligosaccharide chains. Fibroblasts from a child with the phenotype of homozygous familial hypercholesterolemia showed a disruption in receptor processing. This child has two different mutant alleles at the LDL receptor locus. One allele, inherited from his heterozygous mother, produces an abnormal 120 kd protein that cannot be processed to the mature 160 kd form. The other allele, inherited from his heterozygous father, produces a receptor that is synthesized as an elongated 170 kd precursor which undergoes a 40 kd increase in molecular weight to form an abnormally large receptor of 210 kd.
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U2 - 10.1016/0092-8674(82)90276-8
DO - 10.1016/0092-8674(82)90276-8
M3 - Article
C2 - 6291781
AN - SCOPUS:0020420335
SN - 0092-8674
VL - 30
SP - 715
EP - 724
JO - Cell
JF - Cell
IS - 3
ER -