A new class mutation of low density lipoprotein receptor with altered carbohydrate chains.
In a monensin-resistant mutant (Monr-31) of Chinese hamster ovary cells, the O-linked sugar chains of the low density lipoprotein (LDL) receptor are altered, suggesting a mutation at a Golgi apparatus gene. In a compactin-resistant mutant (MF-2) of Chinese hamster V79 cells, the mature LDL receptor is apparently 5000 daltons smaller; the difference is due to altered glycosylation of O-linked sugar chains. Hybrids between MF-2 and Monr-31 still produced LDL receptor molecules with aberrant sugar chains; thus both mutants are in the same complementation group. Krieger and his colleagues (Krieger, M., Kingsley, D., Sege, R., Hobbie, L., and Kozarsky, K. (1985) Trends. Biochem. Sci. 10, 447-452) have classified Chinese hamster ovary cell mutants with altered LDL receptor structure into four groups: ldlA, ldlB, ldlC, and ldlD. Cell-cell hybrids between their ldl mutants and Monr-31 produced wild type mature LDL receptors with normal molecular sizes, suggesting that these compactin- and monensin-resistant mutants define a new class of LDL receptor mutant. Since both of our mutants are defective in internalization of LDL, we assign them as int mutants. This may imply a further etiology for hypercholesterolemia, and cases can now be examined for such a class.
Shite
S
S
Department of Biochemistry, Oita Medical School, Japan.
Seguchi
T
T
Yoshida
T
T
Kohno
K
K
Ono
M
M
Kuwano
M
M
D000818:Animals; D002460:Cell Line; D006023:Glycoproteins / Q000235:genetics*; D006031:Glycosylation; D006822:Hybrid Cells / Q000378:metabolism; D015151:Immunoblotting; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*
D006023:Glycoproteins; D011973:Receptors, LDL