DEPDC5 haploinsufficiency drives increased mTORC1 signaling and abnormal morphology in human iPSC-derived cortical neurons

Neurobiology of Disease - Tập 143 - Trang 104975 - 2020
Lindsay K. Klofas1, Brittany P. Short2, John P. Snow3, Justine Sinnaeve3, Gabrielle V. Rushing1, Grant Westlake2, Will Weinstein2, Rebecca A. Ihrie1,3,4, Kevin C. Ess1,2,3, Robert P. Carson1,2,5
1Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA
2Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN. USA
3Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
4Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
5Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA

Tài liệu tham khảo

Armstrong, 2017, Heterozygous loss of TSC2 alters p53 signaling and human stem cell reprogramming, Hum. Mol. Genet., 26, 4629, 10.1093/hmg/ddx345 Baldassari, 2016, GATOR1 complex: the common genetic actor in focal epilepsies, J. Med. Genet., 53, 503, 10.1136/jmedgenet-2016-103883 Baldassari, 2019, The landscape of epilepsy-related GATOR1 variants, Genet. Med., 21, 398, 10.1038/s41436-018-0060-2 Baldassari, 2019, Dissecting the genetic basis of focal cortical dysplasia: a large cohort study, Acta Neuropathol., 21 Bar-Peled, 2013, A tumor suppressor complex with GAP activity for the rag GTPases that signal amino acid sufficiency to mTORC1, Science, 340, 1100, 10.1126/science.1232044 Baulac, 2015, Familial focal epilepsy with focal cortical dysplasia due to DEPDC5 mutations, Ann. Neurol., 77, 675, 10.1002/ana.24368 Blair, 2018, Genetically engineered human cortical spheroid models of tuberous sclerosis, Nat. Med., 24, 1568, 10.1038/s41591-018-0139-y Chen, 2018, Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study, JAMA Neurol., 75, 279, 10.1001/jamaneurol.2017.3949 Choo, 2008, Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation, Proc. Natl. Acad. Sci., 105, 17414, 10.1073/pnas.0809136105 Crino, 2015, Focal Cortical Dysplasia, Semin. Neurol., 35, 201, 10.1055/s-0035-1552617 Dawson, 2020, Functional screening of GATOR1 complex variants reveals a role for mTORC1 deregulation in FCD and focal epilepsy, Neurobiol. Dis., 134, 10.1016/j.nbd.2019.104640 De Fusco, 2020, Acute knockdown of Depdc5 leads to synaptic defects in mTOR-related epileptogenesis, Neurobiol. Dis., 139, 10.1016/j.nbd.2020.104822 Dehmelt, 2005, The MAP2/tau family of microtubule-associated proteins, Genome Biol., 6, 204, 10.1186/gb-2004-6-1-204 D’Gama, 2015, Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia, Ann. Neurol., 77, 720, 10.1002/ana.24357 D’Gama, 2017, Somatic mutations activating the mTOR pathway in dorsal Telencephalic progenitors cause a continuum of cortical dysplasias, Cell Rep., 21, 3754, 10.1016/j.celrep.2017.11.106 Dibbens, 2013, Mutations in DEPDC5 cause familial focal epilepsy with variable foci, Nat. Genet., 45, 546, 10.1038/ng.2599 Fruman, 2017, The PI3K pathway in human disease, Cell, 170, 605, 10.1016/j.cell.2017.07.029 Germain, 2017, Taming human genetic variability: transcriptomic meta-analysis guides the experimental design and interpretation of iPSC-based disease modeling, Stem Cell Rep., 8, 1784, 10.1016/j.stemcr.2017.05.012 Gingras, 1999, Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism, Genes Dev., 13, 1422, 10.1101/gad.13.11.1422 Gingras, 2001, Hierarchical phosphorylation of the translation inhibitor 4E-BP1, Genes Dev., 15, 2852, 10.1101/gad.912401 Hossini, 2016, PI3K/AKT Signaling pathway is essential for survival of induced pluripotent stem cells, PLoS One, 11, 10.1371/journal.pone.0154770 Hu, 2018, Somatic Depdc5 deletion recapitulates electroclinical features of human focal cortical dysplasia type IIA, Ann. Neurol., 84, 140, 10.1002/ana.25272 Hughes, 2017, Knockout of the epilepsy gene Depdc5 in mice causes severe embryonic dysmorphology with hyperactivity of mTORC1 signalling, Sci. Rep., 2017 Hutchinson, 2011, Regulation of ribosomal protein S6 phosphorylation by casein kinase 1 and protein phosphatase 1, J. Biol. Chem., 286, 8688, 10.1074/jbc.M110.141754 Iffland, 2018, DEPDC5 and NPRL3 modulate cell size, filopodial outgrowth, and localization of mTOR in neural progenitor cells and neurons, Neurobiol. Dis., 114, 184, 10.1016/j.nbd.2018.02.013 Irish, 2010, B-cell signaling networks reveal a negative prognostic human lymphoma cell subset that emerges during tumor progression, Proc. Natl. Acad. Sci. U. S. A., 107, 10.1073/pnas.1002057107 Ishida, 2013, Mutations of DEPDC5 cause autosomal dominant focal epilepsies, Nat. Genet., 45, 552, 10.1038/ng.2601 Kaur, 2013, Novel DEPDC5 mutations causing familial focal epilepsy with variable foci identified, Clin. Genet., 84, 341, 10.1111/cge.12239 Klofas, 2020, Prevention of premature death and seizures in a Depdc5 mouse epilepsy model through inhibition of mTORC1, Hum. Mol. Genet., ddaa068 Kotecha, 2010, Web-based analysis and publication of flow cytometry experiments, Curr. Protoc. Cytometry, 53, 10.17.1, 10.1002/0471142956.cy1017s53 Lal, 2014, DEPDC5 mutations in genetic focal epilepsies of childhood, Ann. Neurol., 75, 788, 10.1002/ana.24127 Lee, 2019, Second-hit DEPDC5 mutation is limited to dysmorphic neurons in cortical dysplasia type IIA, Ann. Clin. Transl. Neurol., 6, 1338, 10.1002/acn3.50815 Li, 2017, Abnormal neural progenitor cells differentiated from induced pluripotent stem cells partially mimicked development of TSC2 neurological abnormalities, Stem Cell Rep., 8, 883, 10.1016/j.stemcr.2017.02.020 Li, 2018, Genome-wide CRISPR-KO screen uncovers mTORC1-mediated Gsk3 regulation in naive pluripotency maintenance and dissolution, Cell Rep., 24, 489, 10.1016/j.celrep.2018.06.027 Lipton, 2014, The neurology of mTOR, Neuron, 84, 275, 10.1016/j.neuron.2014.09.034 Livak, 2001, Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method, Methods, 25, 402, 10.1006/meth.2001.1262 Manning, 2017, AKT/PKB Signaling: navigating the network, Cell, 169, 381, 10.1016/j.cell.2017.04.001 Marsan, 2016, Depdc5 knockout rat: a novel model of mTORopathy, Neurobiol. Dis., 89, 180, 10.1016/j.nbd.2016.02.010 Martin, 2014, A recurrent mutation in DEPDC5 predisposes to focal epilepsies in the French-Canadian population, Clin. Genet., 86, 570, 10.1111/cge.12311 Nadadhur, 2019, Neuron-glia interactions increase neuronal phenotypes in tuberous sclerosis complex patient iPSC-derived models, Stem Cell Rep., 12, 42, 10.1016/j.stemcr.2018.11.019 Okita, 2011, A more efficient method to generate integration-free human iPS cells, Nat. Methods, 8, 409, 10.1038/nmeth.1591 Picard, 2014, DEPDC5 mutations in families presenting as autosomal dominant nocturnal frontal lobe epilepsy, Neurology, 82, 2101, 10.1212/WNL.0000000000000488 Qin, 2016, 4E-BP1, a multifactor regulated multifunctional protein, Cell Cycle, 15, 781, 10.1080/15384101.2016.1151581 Ribierre, 2018, Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia-associated epilepsy, J. Clin. Invest., 128, 2452, 10.1172/JCI99384 Roux, 2007, RAS/ERK signaling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates cap-dependent translation, J. Biol. Chem., 282, 14056, 10.1074/jbc.M700906200 Rozengurt, 2014, Suppression of feedback loops mediated by PI3K/mTOR induces multiple overactivation of compensatory pathways: an unintended consequence leading to drug resistance, Mol. Cancer Ther., 13, 2477, 10.1158/1535-7163.MCT-14-0330 Rushing, 2019, Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis, Life Sci. All., 2 Saxton, 2017, mTOR Signaling in growth, metabolism, and disease, Cell, 169, 361, 10.1016/j.cell.2017.03.035 Scerri, 2015, Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5, Ann. Clin. Transl. Neurol., 2, 575, 10.1002/acn3.191 Scheffer, 2014, Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations, Ann. Neurol., 75, 782, 10.1002/ana.24126 Shen, 2018, Architecture of the human GATOR1 and GATOR1-rag GTPases complexes, Nature, 556, 64, 10.1038/nature26158 Shen, 2019, Arg-78 of Nprl2 catalyzes GATOR1-stimulated GTP hydrolysis by the rag GTPases, J. Biol. Chem., 294, 2970, 10.1074/jbc.AC119.007382 Shi, 2005, Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade, Mol. Cancer Ther., 4, 1533, 10.1158/1535-7163.MCT-05-0068 Shi, 2012, Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks, Nat. Protoc., 7, 1836, 10.1038/nprot.2012.116 Thoreen, 2009, Rapamycin inhibits mTORC1, but not completely, Autophagy, 5, 725, 10.4161/auto.5.5.8504 Tran, 2015, Long-term Everolimus treatment in individuals with tuberous sclerosis complex: a review of the current literature, Pediatr. Neurol., 53, 23, 10.1016/j.pediatrneurol.2014.10.024 van Kranenburg, 2015, Preliminary functional assessment and classification of DEPDC5 variants associated with focal epilepsy, Hum. Mutat., 36, 200, 10.1002/humu.22723 Winden, 2019, Biallelic mutations in TSC2 Lead to abnormalities associated with cortical tubers in human iPSC-derived neurons, J. Neurosci., 39, 9294, 10.1523/JNEUROSCI.0642-19.2019 Wolfson, 2017, The Dawn of the age of amino acid sensors for the mTORC1 pathway, Cell Metab., 26, 301, 10.1016/j.cmet.2017.07.001 Yuskaitis, 2018, A mouse model of DEPDC5-related epilepsy: neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility, Neurobiol. Dis., 111, 91, 10.1016/j.nbd.2017.12.010 Yuskaitis, 2019, Chronic mTORC1 inhibition rescues behavioral and biochemical deficits resulting from neuronal Depdc5 loss in mice, Hum. Mol. Genet., 28, 2952, 10.1093/hmg/ddz123