P1–422: FRET analysis of amyloid precursor protein, presenilin 1 and Grb2 interactionsстатья из журнала
Аннотация: Alzheimer's disease (AD) is a neurodegenerative disorder whose causes are unknown. Autosomal dominant familial AD (FAD) is associated with mutations in either amyloid precursor protein (APP), or presenilin 1 and 2 (PS), genes. APP is a transmembrane protein detectable in different intracellular compartments and at the cell surface. Its proteolytic processing generates Aβ peptides, which are considered neurotoxic and responsible for the neurodegeneration. Presenilins are multipass membrane proteins, involved in the enzymatic cleavage of Notch, ErbB4 and APP. Their role in AD development seems related to the formation of Aβ, although their physiological function, their reciprocal interaction and the molecular mechanisms leading to the neurodegeneration are largely unclear and widely debated. Both proteins are also involved in multiple interactions with different intracellular proteins, the significance of which for AD development is under investigation. Grb2 is a protein involved in cell signaling related to proliferation, apoptosis and cell differentiation recently identified as APP interactor. Its interaction with APP is modulated by the tyrosine phosphorylation of APP C–terminus and is enhanced in the brain of AD patients, suggesting a pathogenic correlation. In this work we show a new interaction between APP, Grb2 and PS1, in human neuroglioma cells (H4). By coimmunoprecipitation, confocal microscopy and by fluorescence resonance energy transfer (FRET) experiments, we show that Grb2 interacts with both APP and PS1. The confocal microscopic analysis reveals extensive colocalization in different cells compartment of APP, Grb2 and PS1. FRET data suggest a close interaction between them. Thus, Grb2 represents the first adaptor protein known to interact with both gene products responsible for AD development, suggesting that both proteins may be part of a common signaling event. The study of APP–Presenilin–Grb2 interaction might provide a good opportunity to light up on the physio–pathological function of APP and Presenilins.
Год издания: 2006
Авторы: Mario Nizzari, Valentina Venezia, Paolo Bianchini, Valentina Caorsi, Alberto Diaspro, Emanuela Repetto, Stefano Thellung, Alessandro Corsaro, Gennaro Schettini, Carlo Tacchetti, Cristina Galliani, Pia Carlo, Tullio Florio, Claudio Russo
Издательство: Wiley
Источник: Alzheimer s & Dementia
Ключевые слова: Alzheimer's disease research and treatments
Открытый доступ: closed
Том: 2
Выпуск: 3S_Part_8