Ruprecht-Karls-University of Heidelberg, Germany, PhD thesis in the research group of Prof. Dr. Dr. h.c. K. Beyreuther at the Center of Molecular Biology Heidelberg (ZMBH), Germany
|2004/2005||Teaching Ruprecht-Karls-University of Heidelberg, Germany, Degree dissertation in the research group of Prof. Dr. Dr. h.c. K. Beyreuther at the Center of Molecular Biology Heidelberg (ZMBH)
Title: Analysis of APP subcellular transport in neurons
|1999-2005||Ruprecht-Karls-University of Heidelberg, Germany, Degree student in biology. Main subjects: molecular biology, cell biology and zoology, Final grade: 1,3 (=First class)|
|1990-1999||High school leaving certificate, Carl-Benz-Gymnasium in Ladenburg
Final grade: 1,8 (=First class)
One of the main characteristics in Alzheimer´s disease are senile plaques. They are mainly composed of a short peptide (b-Amyloid, Ab) derived from the amyloid precursor protein (APP). APP is cleaved by either the a-secretase or, alternatively, by the b-secretase followed by the subsequent cleavage of g-secretase, which leads to the release of Ab or the non-amyloidogenic p3, respectively. As the different secretases are located in distinct subcellular compartments, a change in APP trafficking affects the time that APP spends together with α- or β-secretase in a common compartment and thereby influences its processing. Therefore it is of great interest to investigate the molecular mechanisms underlying the control of APP transport.
For the regulation of cellular transport processes intracellular protein sorting motifs play a crucial role. For APP two of such motifs are known: the 665YTSI668 and 692NPTY695. In a recent study we showed that PAT1a (Protein Interacting with APP Tail 1a) interacts with one of the two putative endocytosis motifs, 665YTSI668(BaSS), of APP and thereby affects APP surface levels as well as APP processing. Recently, we identified a Rab5 GDP/GTP exchange factor, RME-6, as a novel putative binding partner of PAT1a, possibly linking APP to the Rab5 dependent transport machinery of the cell.
Within my PhD thesis I investigate the influence of PAT1a and RME-6 on APP transport and sorting in the cell. Therefore I work on the one hand with cell types showing no asymmetric organization (non-polar cells) and on the other hand with polar cells e.g. nerve cells containing on both axons and dendrites as cellular protrusions. These studies will give deeper insights in the molecular mechanisms of transport, sorting and processing of APP and will thereby contribute to a better under- standing in cellular mechanisms forming the basis of the formation and progression in Alzheimer´s disease.