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Project

Exploring the endocytic route of ICAM-5 in hippocampal neurons - a strategy to reveal the y-secretase independent role of presenilin 1 in trafficking.

Presenilin 1 (PSEN1) is the catalytic component of the gamma-secretase complex involved in the intramembrane proteolysis of the APP C-terminal fragment resulting in the production of amyloid beta peptides. However, PSENs harbor additional functions independent from gamma-secretase. For instance in PSEN1-/- hippocampal neurons, the adhesion molecule ICAM-5 accumulates in degradative organelles, implying a role for PSEN1 in endosomal sorting and organelle turnover. To further corroborate this finding we aim to identify and characterize the endocytic route affected in PSEN1-/- neurons, using ICAM-5 as a read-out molecule. This will be addressed by co-localization studies and live imaging of tagged proteins in combination with transport blocking mutants in primary neurons. This knowledge will allow us to develop bioconjugated superparamagnetic nanoparticles to target and load ICAM-5-positive endosomal compartments. Subcellular proteomics of isolated organelles will generate full protein inventories allowing the identification of novel regulators of endosomal trafficking as well as novel early biomarkers for Alzheimers disease.
Date:1 Jan 2009 →  31 Dec 2011
Keywords:hippocampal neurons
Disciplines:Laboratory medicine, Medical systems biology, Molecular and cell biology