title: Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap.
abstract: Ras signaling has been shown to play an important role in promoting cell survival in many different tissues. Here we show that upregulation of Ras activity in adult Drosophila neurons induces neuronal cell death, as evident from the phenotype of vacuolar peduncle (vap) mutants defective in the Drosophila RasGAP gene, which encodes a Ras GTPase-activating protein. These mutants show age-related brain degeneration that is dependent on activation of the EGF receptor signaling pathway in adult neurons, leading to autophagic cell death (cell death type 2). These results provide the first evidence for a requirement of Egf receptor activity in differentiated adult Drosophila neurons and show that a delicate balance of Ras activity is essential for the survival of adult neurons.
authors.affiliation: Lehrstuhl für Entwicklungsbiologie, Universität Regensburg, 93040 Regensburg, Germany. jose.botella-munoz@biologie.uni-regensburg.de
authors.forename: José A
authors.initials: JA
authors.lastname: Botella
authors.forename: Doris
authors.initials: D
authors.lastname: Kretzschmar
authors.forename: Claudia
authors.initials: C
authors.lastname: Kiermayer
authors.forename: Pascale
authors.initials: P
authors.lastname: Feldmann
authors.forename: David A
authors.initials: DA
authors.lastname: Hughes
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneuwly
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D009154:Mutation; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D020703:ras GTPase-Activating Proteins; D066246:ErbB Receptors