title: A genetic model to dissect the role of Tsc-mTORC1 in neuronal cultures.
abstract: Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in either of two genes, TSC1 or TSC2, whose protein products form a complex that is essential in the regulation of mammalian target of rapamycin (mTOR) activity. TSC is characterized by the presence of benign tumors called hamartomas, which within the brain are known as cortical tubers. Neurological manifestations in TSC patients include epilepsy, mental retardation, and autistic features. In response to hormones, growth factors, or nutrients, the phosphatidylinositol 3-kinase or extracellular signal-regulated kinase-Tsc-mTOR pathways activate the translation machinery and regulate cell growth and/or size. Loss of TSC1 or TSC2 function results in constitutive activation of mTOR leading to tumor formation. Nevertheless, regulation of mTOR activity in nondividing neuronal cells and roles of mTOR hyperactivation in the neurological aspects of TSC remain elusive. Here, we have established a genetic model of mTOR complex 1 (mTORC1) activation in culture by using lentiviral vector-mediated TSC2 knockdown, which offers a reliable tool for analyzing the TSC-mTORC1 signaling in neurons.
authors: Department of Neurology, The F.M. Kirby Neurobiology Center, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors: Duyu
authors: D
authors: Nie
authors: Mustafa
authors: M
authors: Sahin
mesh_terms: D001921:Brain / Q000473:pathology; D048429:Cell Size; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D016086:Lentivirus; D000076222:Mechanistic Target of Rapamycin Complex 1; D008957:Models, Genetic; D046912:Multiprotein Complexes; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D011506:Proteins; D034741:RNA, Small Interfering; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases