title: Phosphorylation of Fe65 amyloid precursor protein-binding protein in response to neuronal differentiation.
abstract: Fe65 is a brain enriched multi domain adaptor protein involved in diverse cellular functions. One of its binding partners is the amyloid-β (Aβ) precursor protein (APP), which after sequential proteolytic processing by secretases gives rise to the Alzheimer's Aβ peptide. Fe65 binds to the APP intracellular domain (AICD). Several studies have indicated that Fe65 binding promotes the amyloidogenic processing of APP. It has previously been shown that expression of APP increases concomitantly with a shift of its processing to the non-amyloidogenic pathway during neuronal differentiation. In this study we wanted to investigate the effects of neuronal differentiation on Fe65 expression. We observed that differentiation of SH-SY5Y human neuroblastoma cells induced by retinoic acid (RA), the phorbol ester PMA, or the γ-secretase inhibitor DAPT resulted in an electrophoretic mobility shift of Fe65. Similar effects were observed in rat PC6.3 cells treated with nerve growth factor. The electrophoretic mobility shift was shown to be due to phosphorylation. Previous studies have shown that Fe65 phosphorylation can prevent the APP-Fe65 interaction. We propose that phosphorylation is a way to modify the functions of Fe65 and to promote the non-amyloidogenic processing of APP during neuronal differentiation.
authors.affiliation: Stockholm University, Department of Neurochemistry, 10691 Stockholm, Sweden.
authors.forename: Niina A
authors.initials: NA
authors.lastname: Koistinen
authors.affiliation: Stockholm University, Department of Neurochemistry, 10691 Stockholm, Sweden.
authors.forename: Smaranda
authors.initials: S
authors.lastname: Bacanu
authors.affiliation: Stockholm University, Department of Neurochemistry, 10691 Stockholm, Sweden. Electronic address: kerstin@neurochem.su.se.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Iverfeldt
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: C091042:APBB1 protein, human; D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014212:Tretinoin; D010664:Phenylmethylsulfonyl Fluoride; D013755:Tetradecanoylphorbol Acetate
keywords: Fe65; Neuroblastoma cells; Phorbol ester; Phosphorylation; Retinoic acid; γ-secretase