Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.
The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified. We show here that in a central nervous system-derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa protein that regulates ligand binding to the low density lipoprotein receptor-related protein (LRP). Anti-LRP antibody also completely abolished the neurite-promoting effect of apoE3. Understanding isoform-specific cell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease pathogenesis.
Holtzman
D M
DM
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Pitas
R E
RE
Kilbridge
J
J
Nathan
B
B
Mahley
R W
RW
Bu
G
G
Schwartz
A L
AL
D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000378:metabolism*; D002232:Carbocyanines; D002460:Cell Line; D003432:Cross-Linking Reagents; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D002232:Carbocyanines; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011994:Recombinant Proteins; C024286:3,3'-dioctadecylindocarbocyanine