the small gtpase rheb affects central brain neuronal morphology and memory formation in drosophila小gtpase rheb影响中央在果蝇大脑神经元形态和记忆形成.pdfVIP

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the small gtpase rheb affects central brain neuronal morphology and memory formation in drosophila小gtpase rheb影响中央在果蝇大脑神经元形态和记忆形成.pdf

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the small gtpase rheb affects central brain neuronal morphology and memory formation in drosophila小gtpase rheb影响中央在果蝇大脑神经元形态和记忆形成

The Small GTPase Rheb Affects Central Brain Neuronal Morphology and Memory Formation in Drosophila 1¤a 2¤b 1 ¤c Heather L. D. Brown , Karla R. Kaun , Bruce A. Edgar * 1 Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 2 Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America 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. Citation: Brown HLD, Kaun KR, Edgar BA (2012) The Small GTPase Rheb Affects Central Brain Neuronal Morphology and Memory Formation in Drosophila. PLoS ONE 7(9): e44888. doi:10.1371/journal.pone.0044888 Editor: Shree Ram Singh, National Cancer