Neurobiology of Disease Tuberous Sclerosis Complex Activity Is Required to Control Neuronal Stress Responses in an mTOR-Dependent Manner
نویسندگان
چکیده
Alessia Di Nardo,1 Ioannis Kramvis,1 Namjik Cho,1 Abbey Sadowski,1 Lynsey Meikle,2 David J. Kwiatkowski,2 and Mustafa Sahin1 1The F. M. Kirby Neurobiology Center, Department of Neurology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, and 2Division of Translational Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
منابع مشابه
Tuberous sclerosis complex activity is required to control neuronal stress responses in an mTOR-dependent manner.
Tuberous sclerosis complex (TSC) is a neurogenetic disorder caused by loss-of-function mutations in either the TSC1 or TSC2 genes and frequently results in prominent CNS manifestations, including epilepsy, mental retardation, and autism spectrum disorder. The TSC1/TSC2 protein complex plays a major role in controlling the Ser/Thr kinase mammalian target of rapamycin (mTOR), which is a master re...
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Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participat...
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Mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 predispose to angiomyolipomas and lymphangioleiomyomatosis in a mTOR-dependent manner. In these mesenchymal lesions, mTOR suppresses macroautophagy-mediated lysosomal degradation of YAP, which is a transcriptional coactivator of Hippo pathway and is required for the tumorigenesis of TSC. Therapeutic applications for TSC and other diseases...
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Abnormal dendritic complexity is a shared feature of many neurodevelopmental disorders associated with neurological defects. Here, we found that the actin-crosslinking protein filamin A (FLNA) is overexpressed in tuberous sclerosis complex (TSC) mice, a PI3K-mTOR model of neurodevelopmental disease that is associated with abnormal dendritic complexity. Both under- and overexpression of FLNA in ...
متن کاملRegulation of mTOR and cell growth in response to energy stress by REDD1.
The tuberous sclerosis tumor suppressors TSC1 and TSC2 regulate the mTOR pathway to control translation and cell growth in response to nutrient and growth factor stimuli. We have recently identified the stress response REDD1 gene as a mediator of tuberous sclerosis complex (TSC)-dependent mTOR regulation by hypoxia. Here, we demonstrate that REDD1 inhibits mTOR function to control cell growth i...
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تاریخ انتشار 2009