Analysis of the zinc-dependent functions of the brain-specific protein APLP1

• Applicant: Dr. Daniela Kaden
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: Funded in 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 177379922

The amyloid precursor protein (APP) that is a critical component in Alzheimer’s disease, belongs to a large protein family, including the brain-specific protein APLP1, which physiological functions are not fully understood. The APP family proteins are described as putative cell-surface receptors and may exert functions in cell-cell and/or cell-cellular matrix interactions. This is underlined by evidences that APP and the APLPs are involved in cis oligomerization and that APLP1 also mediates cell-cell contacts by trans interactions. Recent findings suggest a novel zinc-dependent function of APLP1 by enhancing cis and trans interactions of APLP1 at physiological concentrations.The aim of this project is to unravel the in vivo functions of APLP1 in mouse models with a specific focus on the question how these functions depend on zinc. Therefore I will perform live cell imaging studies in the presence or absence of ligands as well as electrophysiological recordings with primary neurons and hippocampal slices. Additional biochemical analysis will complement the in vivo and in vitro data. Further I want to investigate the phenotypical changes of APLP1 knock-out mice in regard to neuronal abnormalities. Thus I will contribute to the understanding of the neuronal functions of APLP1, its possible involvements in synaptic signaling events and the role APLP1 has within the APP family.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Peter St George-Hyslop