GATOR opathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations

mTOR Hyperactivity Levels Influence the Severity of Epilepsy and Associated Neuropathology in an Experimental Model of Tuberous Sclerosis Complex and Focal Cortical Dysplasia

(2019) Lena H. Nguyen et al.   JOURNAL OF NEUROSCIENCE

Biallelic mutations in SZT2 cause a discernible clinical entity with epilepsy, developmental delay, macrocephaly and a dysmorphic corpus callosum

(2018) Yuji Nakamura et al.   BRAIN & DEVELOPMENT

A novel homozygous mutation in SZT2 gene in Saudi family with developmental delay, macrocephaly and epilepsy

(2018) Muhammad Imran Naseer et al.   Genes & Genomics

GATOR1-dependent recruitment of FLCN–FNIP to lysosomes coordinates Rag GTPase heterodimer nucleotide status in response to amino acids

(2018) Jin Meng et al.   JOURNAL OF CELL BIOLOGY

Second-hit mosaic mutation in mTORC1 repressor DEPDC5 causes focal cortical dysplasia–associated epilepsy

(2018) Théo Ribierre et al.   JOURNAL OF CLINICAL INVESTIGATION

Architecture of the human GATOR1 and GATOR1–Rag GTPases complexes

(2018) Kuang Shen et al.   NATURE

A mouse model of DEPDC5 -related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility

(2018) Christopher J. Yuskaitis et al.   NEUROBIOLOGY OF DISEASE

DEPDC5 and NPRL3 modulate cell size, filopodial outgrowth, and localization of mTOR in neural progenitor cells and neurons

(2018) Philip H. Iffland et al.   NEUROBIOLOGY OF DISEASE

Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish

(2018) Hortense de Calbiac et al.   Annals of Clinical and Translational Neurology

Somatic Depdc5 deletion recapitulates electroclinical features of human focal cortical dysplasia type IIA

(2018) Shuntong Hu et al.   ANNALS OF NEUROLOGY

The landscape of epilepsy-related GATOR1 variants

(2018) Sara Baldassari et al.   GENETICS IN MEDICINE

Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy

(2018) Valeria Salinas et al.   European Journal of Medical Genetics

Genomic diagnostics within a medically underserved population: efficacy and implications

(2017) Kevin A Strauss et al.   GENETICS IN MEDICINE

KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1

(2017) Rachel L. Wolfson et al.   NATURE

SAMTOR is anS-adenosylmethionine sensor for the mTORC1 pathway

(2017) Xin Gu et al.   SCIENCE

Variation in a range of mTOR-related genes associates with intracranial volume and intellectual disability

(2017) M. R. F. Reijnders et al.   Nature Communications

Somatic Mutations Activating the mTOR Pathway in Dorsal Telencephalic Progenitors Cause a Continuum of Cortical Dysplasias

(2017) Alissa M. D’Gama et al.   Cell Reports

Knockout of the epilepsy gene Depdc5 in mice causes severe embryonic dysmorphology with hyperactivity of mTORC1 signalling

(2017) James Hughes et al.   Scientific Reports

The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway

(2016) Lynne Chantranupong et al.   CELL

Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia

(2016) Sarah Weckhuysen et al.   EPILEPSIA

GATOR1 complex: the common genetic actor in focal epilepsies

(2016) Sara Baldassari et al.   JOURNAL OF MEDICAL GENETICS

Mechanism of arginine sensing by CASTOR1 upstream of mTORC1

(2016) Robert A. Saxton et al.   NATURE

Depdc5 knockout rat: A novel model of mTORopathy

(2016) Elise Marsan et al.   NEUROBIOLOGY OF DISEASE

Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration

(2016) Tiffany V. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

(2016) Lawrence S. Hsieh et al.   Nature Communications

Structural mechanism for the arginine sensing and regulation of CASTOR1 in the mTORC1 signaling pathway

(2016) Zhongchao Gai et al.   Cell Discovery

Novel homozygous mutation inKPTNgene causing a familial intellectual disability-macrocephaly syndrome

(2015) Sander Pajusalu et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulatorNPRL3

(2015) Joe C. Sim et al.   ANNALS OF NEUROLOGY

Somatic Mutations in theMTORgene cause focal cortical dysplasia type IIb

(2015) Mitsuko Nakashima et al.   ANNALS OF NEUROLOGY

Familial focal epilepsy with focal cortical dysplasia due toDEPDC5mutations

(2015) Stéphanie Baulac et al.   ANNALS OF NEUROLOGY

Mutations in the mammalian target of rapamycin pathway regulatorsNPRL2andNPRL3cause focal epilepsy

(2015) Michael G. Ricos et al.   ANNALS OF NEUROLOGY

PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia

(2015) Laura A. Jansen et al.   BRAIN

mTOR inhibition suppresses established epilepsy in a mouse model of cortical dysplasia

(2015) Lena H. Nguyen et al.   EPILEPSIA

Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTORin vivo

(2015) Xuan Gong et al.   HUMAN MOLECULAR GENETICS

Amino Acid-Dependent mTORC1 Regulation by the Lysosomal Membrane Protein SLC38A9

(2015) Jennifer Jung et al.   MOLECULAR AND CELLULAR BIOLOGY

SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1

(2015) Manuele Rebsamen et al.   NATURE

Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy

(2015) Jae Seok Lim et al.   NATURE MEDICINE

An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development

(2015) Seung Tae Baek et al.   NATURE MEDICINE

Mechanistic Target of Rapamycin (mTOR) in Tuberous Sclerosis Complex-Associated Epilepsy

(2015) Paolo Curatolo   PEDIATRIC NEUROLOGY

Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1

(2015) S. Wang et al.   SCIENCE

Sestrin2 is a leucine sensor for the mTORC1 pathway

(2015) R. L. Wolfson et al.   SCIENCE

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

(2015) Jeong Sig Kim et al.   Scientific Reports

Mutations in mammalian target of rapamycin regulatorDEPDC5cause focal epilepsy with brain malformations

(2014) Ingrid E. Scheffer et al.   ANNALS OF NEUROLOGY

STRAD pseudokinases regulate axogenesis and LKB1 stability

(2014) Biliana O Veleva-Rotse et al.   Neural Development

The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1

(2014) Lynne Chantranupong et al.   Cell Reports

Sestrins Inhibit mTORC1 Kinase Activation through the GATOR Complex

(2014) Anita Parmigiani et al.   Cell Reports

Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures

(2014) Matthew C. Weston et al.   Frontiers in Molecular Neuroscience

Evolving neurobiology of tuberous sclerosis complex

(2013) Peter B. Crino   ACTA NEUROPATHOLOGICA

Biallelic SZT2 Mutations Cause Infantile Encephalopathy with Epilepsy and Dysmorphic Corpus Callosum

(2013) Lina Basel-Vanagaite et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Mutations in KPTN Cause Macrocephaly, Neurodevelopmental Delay, and Seizures

(2013) Emma L. Baple et al.   AMERICAN JOURNAL OF HUMAN GENETICS

The Folliculin Tumor Suppressor Is a GAP for the RagC/D GTPases That Signal Amino Acid Levels to mTORC1

(2013) Zhi-Yang Tsun et al.   MOLECULAR CELL

Mutations of DEPDC5 cause autosomal dominant focal epilepsies

(2013) Saeko Ishida et al.   NATURE GENETICS

Mutations in DEPDC5 cause familial focal epilepsy with variable foci

(2013) Leanne M Dibbens et al.   NATURE GENETICS

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1

(2013) L. Bar-Peled et al.   SCIENCE

Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder

(2013) W. E. Parker et al.   Science Translational Medicine

Graded loss of tuberin in an allelic series of brain models of TSC correlates with survival, and biochemical, histological and behavioral features

(2012) Elizabeth Yuan et al.   HUMAN MOLECULAR GENETICS

De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly

(2012) Jeong Ho Lee et al.   NATURE GENETICS

mTOR: A pathogenic signaling pathway in developmental brain malformations

(2011) Peter B. Crino   TRENDS IN MOLECULAR MEDICINE

STRADα deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice

(2010) Ksenia A. Orlova et al.   JOURNAL OF CLINICAL INVESTIGATION

Biallelic TSC gene inactivation in tuberous sclerosis complex

(2010) P. B. Crino et al.   NEUROLOGY

Rag proteins regulate amino-acid-induced mTORC1 signalling

(2009) Yasemin Sancak et al.   BIOCHEMICAL SOCIETY TRANSACTIONS