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Physiological function of APP dimers: neuronal transport, release and receptor interaction

Fachliche Zuordnung Molekulare Biologie und Physiologie von Nerven- und Gliazellen
Förderung Förderung von 2010 bis 2017
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 138733498
 
APP transport and APP processing have mostly been studied in a unilateral maimer, excluding APP-interacting proteins and their role in APP trafficking. We and others have demonstrated that the Low Density Lipoprotein Receptor Related Protein (LRP1) is involved in APP processing. We have shown that the C-terminal domain of LRP1 through binding to the adaptor protein FE65 is responsible for the modulation of APP processing (DFG Funding PI 379/3-3). Therefore, we will investigate the role of novel LRP1-interacting partners on APP processing. We were able to demonstrate previously that LRP1 and APP form a complex early in the secretory pathway in the way that APP and LRP1 traffic together from the endoplasmatic reticulum to the cell surface and subsequently are intemalized in an LRP1-dependent fashion. Therefore, we will analyze whether LRPl influences the process of APP homo- and heterodimerization. The Pietrzik group has a long-standing expertise in the cell biology and biochemistry of LRP1 and APP processing, while the Kins group provides an excellent expertise in axonal protein trafficking and APP dimerization studies. Due to the complementary expertise of both groups, the functional role of lipoprotein receptors on endogenous APP function will be studied in great detail.
DFG-Verfahren Forschungsgruppen
 
 

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