Medizinische Universität Graz - Research portal
Selected Publication:
Feussner, G; Scharnagl, H; Scherbaum, C; Acar, J; Dobmeyer, J; Lohrmann, J; Wieland, H; März, W.
Apolipoprotein E5 (Glu212-->Lys): increased binding to cell surface proteoglycans but decreased uptake and lysosomal degradation in cultured fibroblasts.
J LIPID RES 1996 37: 1632-1645.
Doi: 10.1016/S0022-2275(20)39106-9
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- März Winfried
- Scharnagl Hubert
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Animals -
- Apolipoproteins E - chemistry
- Binding, Competitive - chemistry
- CHO Cells - cytology
- Cells, Cultured - cytology
- Child - cytology
- Child, Preschool - cytology
- Comparative Study - cytology
- Cricetinae - cytology
- Endocytosis - physiology
- Exons - genetics
- Female - genetics
- Fibroblasts - metabolism
- Heparin - metabolism
- Humans - metabolism
- Hyperlipidemia, Familial Combined - genetics
- Interpersonal Relations - genetics
- Lipoproteins, VLDL - analysis
- Male - analysis
- Middle Aged - analysis
- Pedigree - analysis
- Phenotype - analysis
- Point Mutation - analysis
- Proteoglycans - metabolism
- Research Support, Non-U.S. Gov't - metabolism
- Find related publications in this database (Keywords)
- apolipoprotein E
- atherosclerosis
- lipoprotein metabolism
- structure-function relationship