title: The small GTPase Rheb affects central brain neuronal morphology and memory formation in Drosophila.
abstract: Mutations in either of two tumor suppressor genes, TSC1 or TSC2, cause tuberous sclerosis complex (TSC), a syndrome resulting in benign hamartomatous tumors and neurological disorders. Cellular growth defects and neuronal disorganization associated with TSC are believed to be due to upregulated TOR signaling. We overexpressed Rheb, an upstream regulator of TOR, in two different subsets of D. melanogaster central brain neurons in order to upregulate the Tsc-Rheb-TOR pathway. Overexpression of Rheb in either the mushroom bodies or the insulin producing cells resulted in enlarged axon projections and cell bodies, which continued to increase in size with prolonged Rheb expression as the animals aged. Additionally, Rheb overexpression in the mushroom bodies resulted in deficiencies in 3 hr but not immediate appetitive memory. Thus, Rheb overexpression in the central brain neurons of flies causes not only morphological phenotypes, but behavioral and aging phenotypes that may mirror symptoms of TSC.
authors.affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Heather L D
authors.initials: HL
authors.lastname: Brown
authors.forename: Karla R
authors.initials: KR
authors.lastname: Kaun
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D005260:Female; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008568:Memory; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024521:Mushroom Bodies / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D014157:Transcription Factors / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D009479:Neuropeptides; D000076205:Ras Homolog Enriched in Brain Protein; C490212:Rheb protein, Drosophila; D014157:Transcription Factors; D020559:Monomeric GTP-Binding Proteins