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Genetic inactivation of mTORC1 or mTORC2 in neurons

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mTORC2,but not mTORC1,is required for hippocampal

May 21,2018 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Supplementary Figure 1 mTORC1 activity is undetected in hippocampal CA1 neurons of Raptor fb-KO Genetic inactivation of mTORC1 or mTORC2 in neuronsmTORC2,but not mTORC1,is required for hippocampalMay 21,2018 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Supplementary Figure 1 mTORC1 activity is undetected in hippocampal CA1 neurons of Raptor fb-KO Genetic inactivation of mTORC1 or mTORC2 in neuronsmTORC2 Steals the Spotlight - Laura A.Jansen,2020Genetic mutations that result in unrestrained activation of the cellular PI3K-AKT-mTOR pathway (the mTORopathies) are significant causes of epilepsy,developmental disability,and autism.1 These disorders can result either from loss of function mutations in genes that normally inhibit the pathway (ie,TSC1,TSC2,DEPDC5,PTEN) or from gain of function mutations in genes that activate

mTORC2 Balances AKT Activation and eIF2a Serine 51

to rapamycin or TSC inactivation,respectively,rendering the interpretation of thendings difcult(25,26).Wehaveinves-tigated the regulation of eIF2aS51P in mouse and human cells rendered defective in mTORC1 and/or mTORC2 activity by genetic or pharmacological means.We observed that mTORC2 plays a major role in the inhibition of PERK andmTORC2 Balances AKT Activation and eIF2a Serine 51 to rapamycin or TSC inactivation,respectively,rendering the interpretation of thendings difcult(25,26).Wehaveinves-tigated the regulation of eIF2aS51P in mouse and human cells rendered defective in mTORC1 and/or mTORC2 activity by genetic or pharmacological means.We observed that mTORC2 plays a major role in the inhibition of PERK andmTORC1 and mTORC2 regulate distinct aspects of Aug 15,2019 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;To better understand each complexs role in synaptic transmission,we genetically inactivated mTORC1 or mTORC2 in cultured mouse glutamatergic hippocampal neurons.Inactivation of either complex reduced neuron growth and evoked EPSCs,however,mTORC1 exerted its effects on eEPSCs at the postsynapse and mTORC2 at the presynapse.

mTORC1 and mTORC2 regulate distinct aspects of

Aug 15,2019 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;To better understand each complexs role in synaptic transmission,we genetically inactivated mTORC1 or mTORC2 in cultured mouse glutamatergic hippocampal neurons.Inactivation of either complex reduced neuron growth and evoked EPSCs,however,mTORC1 exerted its effects on eEPSCs at the postsynapse and mTORC2 at the presynapse.mTORC1 and mTORC2 have largely distinct functions in Rap-KO 747 Genetic inactivation of mTORC1 or mTORC2 in neurons#177; 70 Genetic inactivation of mTORC1 or mTORC2 in neurons#181;m,p Genetic inactivation of mTORC1 or mTORC2 in neuronslt; 0.001; Figure 1D),and mTORC2 inactivation (Con 1035 Genetic inactivation of mTORC1 or mTORC2 in neurons#177; 76 Genetic inactivation of mTORC1 or mTORC2 in neurons#181;m,Ric-KO 815 Genetic inactivation of mTORC1 or mTORC2 in neurons#177; 147 78 Genetic inactivation of mTORC1 or mTORC2 in neurons#181;m,p = 0.043; Figure 1H).These data verify that a reduction in mTORC1 or mTORC2 The mTOR-regulated Phosphoproteome Reveals aGenetic inactivation of mTORC1 or mTORC2 in neurons reveals distinct functions in glutamatergic synaptic transmission.McCabe MP,Cullen ER,Barrows

The Neurology of mTOR Neuron

The mTOR signaling pathway,which regulates protein synthesis and cell growth,is crucial for the normal development and function of the nervous system.Lipton and Sahin review the contributions of this pathway to neurological disorders including tuberous sclerosis,autism,Some results are removed in response to a notice of local law requirement.For more information,please see here.Previous123456NextSin1/mTORC2 regulate B cell growth and metabolism by Jan 31,2019 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;According to previous studies by our group and other researchers,inactivation of mTORC2 via the deletion of either Sin1 or Rictor does not impair mTORC1,and in some cases,these changes increase Some results are removed in response to a notice of local law requirement.For more information,please see here.12345NextAblation of the mTORC2 component rictor in brain or One of the essential and unique components of mTORC1 is the protein raptor (regulatory associated protein of mTOR; Kim et al.,2002),whereas the protein rictor (rapamycin-insensitive companion of mTOR) is essential and unique for mTORC2 (Jacinto et al.,2004; Sarbassov et al.,2004).Several lines of evidence indicate that mTORC1 is mainly responsible for cell growth and proliferation in

Some results are removed in response to a notice of local law requirement.For more information,please see here.Sin1/mTORC2 regulate B cell growth and metabolism by

Jan 31,2019 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;According to previous studies by our group and other researchers,inactivation of mTORC2 via the deletion of either Sin1 or Rictor does not impair mTORC1,and in some cases,these changes increase Rapamycin-Resistant mTOR Activity Is Required for Sensory mTORC1 inactivation suppresses Stat3 signaling in DRG neurons induced by a conditioning lesion.A ,Sections of DRGs from WT,mTOR,and Raptor KO mice with or without CL,with p-Stat3 (red) and Tuj1 (green) staining.mTOR or Raptor deletion inhibited p-Stat3 at 3 d after CL.

PCB 95 Promotes Dendritic Growth in Primary Rat

Similarly,both mTORC1 and mTORC2 signaling promote dendritic growth in olfactory bulb neurons (Skalecka et al.2016) and hippocampal neurons (Urbanska et al.2012).Consistent with these observations,inhibition of either mTORC1 or mTORC2 activity by siRNA knockdown of raptor or rictor,respectively,blocked the dendrite promoting activity of Molecular neurobiology of mTOR - ScienceDirectJan 26,2017 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Compared with mTORC2,mTORC1 has been poorly studied in the context of the cytoskeleton,both in non-neuronal cells and in neurons.An initial observation by Choi et al.(2002) demonstrated the rapamycin-dependent phosphorylation of cytoplasmic linker protein of 170 kDa (CLIP-170; a plus-end microtubule-tracking protein).These authors also Molecular neurobiology of mTOR - ScienceDirectJan 26,2017 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Compared with mTORC2,mTORC1 has been poorly studied in the context of the cytoskeleton,both in non-neuronal cells and in neurons.An initial observation by Choi et al.(2002) demonstrated the rapamycin-dependent phosphorylation of cytoplasmic linker protein of 170 kDa (CLIP-170; a plus-end microtubule-tracking protein).These authors also

MTOR (human) Gene Target - PubChem

Signaling through mTORC1 and mTORC2 regulate protein production,which influences cell growth,division,and survival.This mTOR signaling is especially important for growth and development of the brain,and it plays a role in a process called synaptic plasticity,which is the ability of the connections between nerve cells (synapses) to change Loss of Tsc1 accelerates malignant gliomagenesis when Abstract.Glioblastomas frequently harbour genetic lesions that stimulate the activity of mammalian target of rapamycin complex 1 (mTORC1).Loss of heterozygosity of tuberous sclerosis complex 1 (TSC1) or TSC2,which together form a critical negative regulator of mTORC1,is also seen in glioblastoma; however,it is not known how loss of the TSC complex affects the development of malignant gliomas.Inhibition of the IGF-1PI3KAktmTORC2 pathway in lipid The IGF-1Akt pathway is known to be downregulated by psychosine (Cantuti-Castelvetri et al.,2015; Zaka et al.,2005; Teixeira et al.,2014),but the mechanism of this effect is unknown.To examine the dynamics of this regulation,we looked at the intracellular levels of phosphorylated Akt (p-Akt) and p-ERK in conditions where we detected a significant change in cell morphology (Fig.1A,30

Inactivation of mTORC1 in the Developing Brain Causes

May 01,2013 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;The mammalian target of rapamycin (mTOR) regulates cell growth in response to various intracellular and extracellular signals.It assembles into two multiprotein complexes the rapamycin-sensitive mTOR complex 1 (mTORC1) and the rapamycin-insensitive mTORC2.In this study,we inactivated mTORC1 in mice by deleting the gene encoding raptor in the progenitors of theH Genetic inactivation of mTORC1 or mTORC2 in neurons#228;rtig W,Krueger M,Hofmann S,Prei Genetic inactivation of mTORC1 or mTORC2 in neurons#223;ler H,M Genetic inactivation of mTORC1 or mTORC2 in neurons#228;rkel M Genetic inactivation of mTORC1 or mTORC2 in neurons reveals distinct functions in glutamatergic synaptic transmission.McCabe MP,Cullen ER,Barrows CM,Shore AN,Tooke KI,Laprade KA,Stafford JM,Weston MC eLife (2020) 9 ..ICC; tested species mouse ASCL1- and DLX2-induced GABAergic neurons from hiPSC-derived NPCs.Genetic inactivation of mTORC1 or mTORC2 in neurons Mar 03,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;To investigate the effects of mTORC1 or mTORC2 inactivation on neurons,we cultured primary hippocampal neurons isolated from P0-P1 Raptor flox/flox or Rictor flox/flox mice on astrocytes isolated from P0-P1 wild-type mice.At the time of plating,we transduced the neurons with adeno-associated viruses (AAVs) expressing either an mCherry-Cre fusion protein or mCherry alone,both

Genetic Inactivation of mTORC1 or mTORC2 in Neurons

To better understand their roles in synaptic transmission,we genetically inactivated mTORC1 or mTORC2 in cultured mouse glutamatergic hippocampal neurons.Inactivation of either complex reduced neuron growth and evoked EPSCs (eEPSCs),however,the effects of mTORC1 on eEPSCs were postsynaptic and the effects of mTORC2 were presynaptic.Genes Free Full-Text Regulation of mTORC2 SignalingSep 04,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Mammalian target of rapamycin (mTOR),a serine/threonine protein kinase and a master regulator of cell growth and metabolism,forms two structurally and functionally distinct complexes,mTOR complex 1 (mTORC1) and mTORC2.While mTORC1 signaling is well characterized,mTORC2 is relatively poorly understood.mTORC2 appears to exist in functionally distinct pools,but few mTORC2GSK3 Controls mTOR and Prosurvival Signaling in Neurons Despite extensive studies in non-neuronal cells,crosstalk between GSK3 and other signaling pathways remains not well defined in neurons.In the present study,we report that GSK3 positively affected the activity of effectors of mammalian target of rapamycin complex 1 (mTORC1) and complex 2 (mTORC2),in mature neurons in vitro and in vivo.

Expression of the Neuronal tRNA n-Tr20 Regulates Synaptic

The effect of mutations in individual mammalian tRNA genes is unknown.Kapur et al.find that loss of n-Tr20,a brain-specific tRNA,alters signaling pathways regulating translation initiation,causing changes in synaptic transmission and reduced seizure susceptibility.This study highlights the importance of investigating tRNA mutations in disease contexts.DEPDC5 haploinsufficiency drives increased mTORC1 Sep 01,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;iPSCs were generated from epilepsy patients harboring loss-of-function mutations in DEPDC5..DEPDC5 +/ iPSCs and neurons showed mTORC1 hyperactivation and reduced NPRL2 protein..DEPDC5 +/ neurons had enlarged somas,a phenotype rescued with mTORC1 inhibition..Heterozygous DEPDC5 mutations may contribute to disease by driving increased mTORC1 signaling.DEPDC5 haploinsufficiency drives increased mTORC1 Sep 01,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;iPSCs were generated from epilepsy patients harboring loss-of-function mutations in DEPDC5..DEPDC5 +/ iPSCs and neurons showed mTORC1 hyperactivation and reduced NPRL2 protein..DEPDC5 +/ neurons had enlarged somas,a phenotype rescued with mTORC1 inhibition..Heterozygous DEPDC5 mutations may contribute to disease by driving increased mTORC1 signaling.

Complex Neurological Phenotype in Mutant Mice Lacking

Mutations in the TSC1 and TSC2 genes cause tuberous sclerosis complex (TSC),a genetic disease often associated with epilepsy,intellectual disability,and autism,and characterized by the presence of anatomical malformations in the brain as well as tumors in other organs.The TSC1 and TSC2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signaling.Author Matthew P McCabe,Erin R Cullen,Caitlynn M Barrows,Amy N Shore,Katherine I Tooke,Kathryn A LapraPublish Year 2020Sin1/mTORC2 regulate B cell growth and metabolism by Jan 31,2019 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;According to previous studies by our group and other researchers,inactivation of mTORC2 via the deletion of either Sin1 or Rictor does not impair mTORC1,and in some cases,these changes increase Author Matthew P McCabe,Erin R Cullen,Caitlynn M Barrows,Amy N Shore,Katherine I Tooke,Kathryn A LapraPublish Year 2020Genetic inactivation of mTORC1 or mTORC2 in neurons Mar 03,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Genetic inactivation of mTORC1 or mTORC2 in neurons reveals distinct functions in glutamatergic synaptic transmission.McCabe MP(1),Cullen ER(1),Barrows CM(1),Shore AN(1),Tooke KI(1),Laprade KA(1),Stafford JM(1),Weston MC(1).Author information (1)Neurological Sciences,University of Vermont,Burlington,United States.

Author Matthew P McCabe,Erin R Cullen,Caitlynn M Barrows,Amy N Shore,Katherine I Tooke,Kathryn A LapraPublish Year 2020Genetic inactivation of mTORC1 or mTORC2 in neurons

Mar 03,2020 Genetic inactivation of mTORC1 or mTORC2 in neurons#0183;Genetic inactivation of mTORC1 or mTORC2 in neurons reveals distinct functions in glutamatergic synaptic transmission.Matthew P McCabe,Erin R Cullen,Caitlynn M Barrows, Representative images of Raptor-Con (A 1) and Raptor-KO neurons (A 2) showing the structure of the neurons revealed by MAP2 immunofluorescence (purple) Author Matthew P McCabe,Erin R Cullen,Caitlynn M Barrows,Amy N Shore,Katherine I Tooke,Kathryn A LapraPublish Year 2020(PDF) Genetic inactivation of mTORC1 or mTORC2 inGenetic inactivation of mTORC1 or mTORC2 in neurons reveals distinct functions in glutamatergic synaptic transmission

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