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  • Title: Diminished LDL receptor and high heparin binding of apolipoprotein E2 Sendai associated with lipoprotein glomerulopathy.
    Author: Hoffmann MM, Scharnagl H, Panagiotou E, Banghard WT, Wieland H, März W.
    Journal: J Am Soc Nephrol; 2001 Mar; 12(3):524-530. PubMed ID: 11181800.
    Abstract:
    Variants of apolipoprotein E (apoE) have been linked to lipoprotein glomerulopathy, a new glomerular disease characterized by the deposition of lipoproteins in mesangial capillaries. One third of affected patients are heterozygous for apoE2 Sendai (Arg(145) Pro). Variants of apoE can also produce type III hyperlipoproteinemia (HLP). Recessive type III HLP is caused by apoE2 (Arg(158) Cys), a mutant with diminished low-density lipoprotein (LDL) receptor binding but halfnormal heparin binding. Dominant type III HLP is caused by mutations that markedly alter heparin binding but modestly reduce receptor binding. This study examined whether apoE2 Sendai (Arg(145) Pro) was functionally different from type III HLP-producing apoE variants by expressing apoE3, apoE2 (Arg(158) Cys), apoE1 (Arg(146) Glu), a dominant apoE variant, and apoE2 Sendai (Arg(145) Pro) in the baculovirus system. LDL receptor binding was studied using recombinant apoE complexed to phospholipid vesicles and to very lowdensity lipoprotein from a patient with familiar apoE deficiency. Compared with apoE3, receptor-binding activities of apoE2 (Arg(158) Cys), apoE1 (Arg(146) Glu), and apoE2 Sendai (Arg(145) Pro) all were less than 5%. Heparin-binding activities were 53%, 23%, and 66%, respectively, of apoE3. The distribution of apoE2 Sendai among the major plasma lipoprotein fractions was similar to that of apoE3 and apoE2 (Arg(158) Cys). ApoE2 Sendai (Arg(145) Pro) represents the only known mutation within the heparin-binding domain of apoE (residues 142 through 147), revealing diminished receptor binding and almost normal heparin binding. These unique characteristics of apoE2 Sendai (Arg(145) Pro) may relate to the development of lipoprotein glomerulopathy.
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