Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8686396 | Neurobiology of Disease | 2018 | 41 Pages |
Abstract
Neurons exhibiting PS6 immunoreactivity (Ser 235/236) in human specimens were 1.5Ã larger than neurons in post-mortem control samples. DEPDC5/NPRL3 KD caused mTORC1, but not mTORC2, hyperactivation, soma enlargement, and increased filopodia in N2aC and mNPCs compared with wildtype cells. DEPDC5/NPRL3 KD led to inappropriate mTOR localization at the lysosome along with constitutive mTOR activation following amino acid deprivation. DEPDC5/NPRL3 KD effects on morphology and functional mTOR activation were reversed by rapamycin. mTOR-dependent effects of DEPDC5/NPRL3 KD on morphology and subcellular localization of mTOR in neurons suggests that loss-of-function in GATOR1 subunits may play a role in MCD formation during fetal brain development.
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Authors
Philip H. II, Marianna Baybis, Allan E. Barnes, Richard J. Leventer, Paul J. Lockhart, Peter B. Crino,