Apolipoprotein E5 (Glu212→Lys): increased binding to cell surface proteoglycans but decreased uptake and lysosomal degradation in cultured fibroblasts.
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...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 January 1996
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| In: |
Journal of lipid research
Year: 1996, Jahrgang: 37, Heft: 8, Pages: 1632-1645 |
| ISSN: | 1539-7262 |
| DOI: | 10.1016/S0022-2275(20)39106-9 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0022-2275(20)39106-9 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022227520391069 
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| Verfasserangaben: | Giso Feussner, Hubert Scharnagl, Clemens Scherbaum, Jasmin Acar, Jürgen Dobmeyer, Jens Lohrmann, Heinrich Wieland, Winfried März |
| Zusammenfassung: | 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. |
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| Beschreibung: | Im Titel ist "212" tiefgestellt Gesehen am 29.01.2025 Artikelversion: 4. Januar 2021 |
| Beschreibung: | Online Resource |
| ISSN: | 1539-7262 |
| DOI: | 10.1016/S0022-2275(20)39106-9 |