Homer2 and Homer3 interact with amyloid precursor protein and inhibit Abeta production.
The study of Amyloid Precursor Protein (APP) processing has been the focus of considerable interest, since it leads to Abeta peptide generation, the main constituent of neuritic plaques found in brains of Alzheimer's disease patients. Therefore, the identification of novel APP binding partners that regulate Abeta peptide production represents a pharmaceutical target aiming at reducing Alphabeta pathology. In this study, we provide evidence that Homer2 and Homer3 but not Homer1 proteins interact specifically with APP. Their expression inhibits APP processing and reduces secretion of Abeta peptides. In addition, they decrease the levels of cell surface APP and inhibit maturation of APP and beta-secretase (BACE1). The effects of Homer2 and Homer3 on APP trafficking to the cell surface and/or on APP and BACE1 maturation could be part of the mechanism by which the expression of these proteins leads to the significant reduction of Abeta peptide production.
Parisiadou
Loukia
L
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece.
Bethani
Ioanna
I
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece.
Michaki
Vasiliki
V
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece.
Krousti
Kaliopi
K
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece.
Rapti
Georgia
G
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece.
Efthimiopoulos
Spiros
S
Division of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, 157 84 Panepistimiopolis, Ilisia, Athens, Greece. Electronic address: efthis@biol.uoa.gr.
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D000072233:Homer Scaffolding Proteins; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; C000606614:HOMER1 protein, human; C000606616:HOMER3 protein, human; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; C000606625:Homer2 protein, mouse; C000606627:Homer3 protein, mouse