title: Megalin interacts with APP and the intracellular adapter protein FE65 in neurons.
abstract: Increasing evidence has implicated megalin, a low-density lipoprotein receptor-related protein, in the pathogenesis of Alzheimer's disease (AD). In the brain, megalin is expressed in brain capillaries, ependymal cells and choroid plexus, where it participates in the clearance of brain amyloid β-peptide (Aβ) complex. Recently, megalin has also been detected in oligodendrocytes and astrocytes. In this study we demonstrate that megalin is widely distributed in neurons throughout the brain. Additionally, given that FE65 mediates the interaction between the low density lipoprotein receptor-related protein-1 and the amyloid precursor protein (APP) to modulate the rate of APP internalization from the cell surface, we hypothesize that megalin could also interact with APP in neurons. Our results confirm that megalin interacts with APP and FE65, suggesting that these three proteins form a tripartite complex. Moreover, our findings imply that megalin may participate in neurite branching. Taken together, these results indicate that megalin has an important role in Aβ-mediated neurotoxicity, and therefore may be involved in the neurodegenerative processes that occur in AD.
authors.affiliation: Laboratory of Neuroscience, Research Center, Hospital 12 de Octubre, 28041 Madrid, Spain.
authors.forename: Ximena
authors.initials: X
authors.lastname: Alvira-Botero
authors.forename: Rocío
authors.initials: R
authors.lastname: Pérez-Gonzalez
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Teo
authors.initials: T
authors.lastname: Vargas
authors.forename: Desiree
authors.initials: D
authors.lastname: Antequera
authors.forename: Miguel
authors.initials: M
authors.lastname: Garzón
authors.forename: Felix
authors.initials: F
authors.lastname: Bermejo-Pareja
authors.forename: Eva
authors.initials: E
authors.lastname: Carro
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; C486243:Apbb1 protein, mouse; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins