The Low‐Density Lipoprotein Receptor‐Related Protein, a Multifunctional Apolipoprotein E Receptor, Modulates Hippocampal Neurite Development

• Published in: Journal of neurochemistry Vol. 68; no. 2; pp. 587 - 595
• Main Authors: Narita, Masaaki, Bu, Guojun, Holtzman, David M., Schwartz, Alan L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.1997; Blackwell
• Subjects: 39‐kDa protein; Alzheimer's disease; Animals; Antibodies - pharmacology; Apolipoprotein E; Apolipoprotein E‐deficient mice; Apolipoproteins - analysis; Apolipoproteins - physiology; Astrocytes - chemistry; Astrocytes - physiology; Biological and medical sciences; Blood Proteins - pharmacology; Carrier Proteins - analysis; Carrier Proteins - pharmacology; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured - chemistry; Cells, Cultured - physiology; Fetus - cytology; Fundamental and applied biological sciences. Psychology; Glycoproteins - analysis; Glycoproteins - pharmacology; Hippocampus - cytology; Isolated neuron and nerve. Neuroglia; LDL-Receptor Related Protein-Associated Protein; Ligands; Lipoprotein receptor‐related protein; Low Density Lipoprotein Receptor-Related Protein-1; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Chaperones - analysis; Neurite outgrowth; Neurites - chemistry; Neurites - physiology; Neurons - chemistry; Neurons - ultrastructure; Rabbits; Receptors, Immunologic - analysis; Receptors, Immunologic - immunology; Receptors, Immunologic - physiology; Receptors, LDL - analysis; Receptors, LDL - physiology; Receptors, Lipoprotein - analysis; Receptors, Lipoprotein - physiology; Subcellular Fractions - chemistry; Vertebrates: nervous system and sense organs; Neurite; Alzheimer disease; Rodentia; Central nervous system; In vitro; Lipoprotein LDL; Vertebrata; Mammalia; Neuron; Mouse; Apolipoprotein E; Development; Hippocampus; Brain (vertebrata); Biological receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1997.68020587.x

: The ε4 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.