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.
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Acknowledgments
We are grateful to Alessia Di Nardo and Emily Greene-Colozzi for critical reading of the manuscript. Work in the Sahin laboratory is supported in part by grants from the NIH (R01 NS58956), the John Merck Scholars Fund, Tuberous Sclerosis Alliance, and Children’s Hospital Boston Translational Research Program to M.S., and the Children’s Hospital Boston Mental Retardation and Developmental Disabilities Research Center (P30 HD18655). D.N. was supported by a Mentor Based Postdoctoral Fellowship from Autism Speaks.
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Nie, D., Sahin, M. (2012). A Genetic Model to Dissect the Role of Tsc-mTORC1 in Neuronal Cultures. In: Weichhart, T. (eds) mTOR. Methods in Molecular Biology, vol 821. Humana Press. https://doi.org/10.1007/978-1-61779-430-8_25
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DOI: https://doi.org/10.1007/978-1-61779-430-8_25
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