The low-density lipoprotein receptor-related protein, a multifunctional apolipoprotein E receptor, modulates hippocampal neurite development.
The epsilon 4 allele of apolipoprotein E (apoE) is an important risk factor for Alzheimer's disease. A major neuronal receptor for apoE within the brain is the low-density lipoprotein receptor-related protein (LRP). Using primary cultured hippocampal neurons, we examined the role of LRP in early neuronal development. LRP, as well as a 39-kDa protein that regulates its activity, is localized abundantly in developing neurons. Both the 39-kDa protein and an anti-LRP antibody inhibited neurite outgrowth of primary hippocampal neurons cultured in either serum-containing medium or on cortical astrocyte monolayers in serum-free medium. It is noteworthy that microtubule-associated protein-2 immunoreactive process outgrowth was decreased significantly in hippocampal neurons cultured on cortical astrocytes derived from apoE-deficient mice and was not diminished further following incubation with LRP inhibitors. Thus, these results suggest that LRP can influence aspects of neuronal process development and that apoE-containing lipoproteins may be one of the major LRP ligands that can contribute to this process.
Narita
M
M
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Bu
G
G
Holtzman
D M
DM
Schwartz
A L
AL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001053:Apolipoproteins / Q000032:analysis / Q000502:physiology; D001253:Astrocytes / Q000737:chemistry / Q000502:physiology; D001798:Blood Proteins / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000737:chemistry / Q000502:physiology; D005333:Fetus / Q000166:cytology; D006023:Glycoproteins / Q000032:analysis / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018832:Molecular Chaperones / Q000032:analysis; D016501:Neurites / Q000737:chemistry* / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D011817:Rabbits; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011973:Receptors, LDL / Q000032:analysis / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000032:analysis / Q000502:physiology*; D013347:Subcellular Fractions / Q000737:chemistry
D000906:Antibodies; D001053:Apolipoproteins; D001798:Blood Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D026563:LDL-Receptor Related Protein-Associated Protein; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018832:Molecular Chaperones; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein