title: Shedding of APP limits its synaptogenic activity and cell adhesion properties.
abstract: The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) and has essential synapse promoting functions. Synaptogenic activity as well as cell adhesion properties of APP presumably depend on trans-cellular dimerization via its extracellular domain. Since neuronal APP is extensively processed by secretases, it raises the question if APP shedding affects its cell adhesion and synaptogenic properties. We show that inhibition of APP shedding using cleavage deficient forms of APP or a dominant negative α-secretase strongly enhanced its cell adhesion and synaptogenic activity suggesting that synapse promoting function of APP is tightly regulated by α-secretase mediated processing, similar to other trans-cellular synaptic adhesion molecules.
authors.affiliation: Center of Molecular Biology ZMBH, University of Heidelberg Heidelberg, Germany ; Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich Munich, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Stahl
authors.affiliation: Department of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schilling
authors.affiliation: Center of Molecular Biology ZMBH, University of Heidelberg Heidelberg, Germany ; Center for Molecular Neurobiology (ZMNH), University of Hamburg Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Soba
authors.affiliation: Department of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rupp
authors.affiliation: Deutsches Institut für DemenzPrävention, Experimental Neurology, Saarland University Homburg/Saar, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
authors.affiliation: Center of Molecular Biology ZMBH, University of Heidelberg Heidelberg, Germany ; Department of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Center of Molecular Biology ZMBH, University of Heidelberg Heidelberg, Germany ; Department of Biosystems Science and Engineering, ETH Zürich Basel, Switzerland.
authors.forename: Gunter
authors.initials: G
authors.lastname: Merdes
authors.affiliation: Department of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Eggert
authors.affiliation: Center of Molecular Biology ZMBH, University of Heidelberg Heidelberg, Germany ; Department of Human Biology and Human Genetics, Technical University of Kaiserslautern Kaiserslautern, Germany ; Deutsches Institut für DemenzPrävention, Experimental Neurology, Saarland University Homburg/Saar, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kins
keywords: APP processing; Alzheimer’s disease; SAM; amyloid precursor protein; cell adhesion; synaptogenic activity