Apolipoprotein E5 (Glu212→Lys)

• Verfasst von: Feussner, Giso [VerfasserIn]
• Verfasst von: Scharnagl, Hubert [VerfasserIn]
• Verfasst von: Scherbaum, Clemens [VerfasserIn]
• Verfasst von: Acar, Jasmin [VerfasserIn]
• Verfasst von: Dobmeyer, Jürgen [VerfasserIn]
• Verfasst von: Lohrmann, Jens Dieter Wolfgang [VerfasserIn]
• Verfasst von: Wieland, Heinrich [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Titel: Apolipoprotein E5 (Glu212→Lys)
• Titelzusatz: increased binding to cell surface proteoglycans but decreased uptake and lysosomal degradation in cultured fibroblasts.
• Verf.angabe: Giso Feussner, Hubert Scharnagl, Clemens Scherbaum, Jasmin Acar, Jürgen Dobmeyer, Jens Lohrmann, Heinrich Wieland, Winfried März
• E-Jahr: 1996
• Jahr: 1 January 1996
• Umfang: 14 S.
• Fussnoten: Im Titel ist "212" tiefgestellt ; Gesehen am 29.01.2025 ; Artikelversion: 4. Januar 2021
• Titel Quelle: Enthalten in: Journal of lipid research
• Ort Quelle: Amsterdam : Elsevier, 1959
• Jahr Quelle: 1996
• Band/Heft Quelle: 37(1996), 8, Seite 1632-1645
• ISSN Quelle: 1539-7262
• DOI: doi:10.1016/S0022-2275(20)39106-9
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1915926416

Abstract

A new apolipoprotein (apo) E variant, apoE5 (Glu212->Lys) was identified in a Turkish family. The variant was due to a point mutation (CAG->AAG) at the first nucleotide position of the codon encoding amino acid residue 212 of the mature apoE. The 23-year-old index patient was heterozygous for the mutation. Examination of the proband's kindred revealed six heterozygous and two homozygous mutation carriers. Compared to non-carriers, carriers of the mutation had slightly higher triglycerides (1.25 versus 1.11 g/l) and lower HDL cholesterol (0.36 versus 0.41 g/l). Very low density lipoproteins (VLDL) from an apoE5 (Glu212->Lys) homozygote displayed enhanced binding (+17%, P < 0.05), but decreased uptake (-35%, P < 0.0001) and degradation (-51%, P < 0.0001) in cultured fibroblasts, compared to E3/3-VLDL. The region of the apoE molecule surrounding residue 212 contains a heparin binding domain. Consistently, the enhanced cell surface binding of E5/5-VLDL was observed in “wild-type” Chinese hamster ovary cells (+19%, P < 0.05), but not in proteoglycan-deficient cells. The binding of E5/5-VLDL to heparin was increased (+22%, P < 0.05). As the endocytosis of apoE-containing particles involves the transfer of proteoglycan-bound ligands to lipoprotein receptors, the stronger binding of apoE5 (Glu212->Lys) to proteoglycans could reduce the rate at which the mutant is finally delivered to endocytotic pathways. These data may provide evidence for a functionally important heparin binding site around amino acid residue 212 of the apoE molecule in vivo.