Apolipoprotein E5 (Glu212–>Lys): increased binding to cell surface proteoglycans but decreased uptake and lysosomal degradation in cultured fibroblasts.

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 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.