ArticleScientific reports2014
Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Reducing Filamin A Restores Cortical Synaptic Connectivity and Early Social Communication Following Cellular Mosaicism in Autism Spectrum Disorder Pathways.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Unraveling the Role of Ras Homolog Enriched in Brain (Rheb1 and Rheb2): Bridging Neuronal Dynamics and Cancer Pathogenesis through Mechanistic Target of Rapamycin Signaling.International journal of molecular sciences · 2024Review
- Microtubule Cytoskeletal Network Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders.International journal of molecular sciences · 2023Article
- A Farnesyltransferase Inhibitor Restores Cognitive Deficits inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Shared mechanisms of neural circuit disruption in tuberous sclerosis across lifespan: Bridging neurodevelopmental and neurodegenerative pathology.Frontiers in genetics · 2022Review
- mTOR-Dependent Spine Dynamics in Autism.Frontiers in molecular neuroscience · 2022Review
- Connecting the Neurobiology of Developmental Brain Injury: Neuronal Arborisation as a Regulator of Dysfunction and Potential Therapeutic Target.International journal of molecular sciences · 2021Review
- Rheb mediates neuronal-activity-induced mitochondrial energetics through mTORC1-independent PDH activation.Developmental cell · 2021Article
- Axon growth and synaptic function: A balancing act for axonal regeneration and neuronal circuit formation in CNS trauma and disease.Developmental neurobiology · 2020Review
- Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells.Molecular autism · 2020Review
- Syntenin: PDZ Protein Regulating Signaling Pathways and Cellular Functions.International journal of molecular sciences · 2019Review
- Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.Experimental neurobiology · 2019Article
- Neuron-Glia Interactions Increase Neuronal Phenotypes in Tuberous Sclerosis Complex Patient iPSC-Derived Models.Stem cell reports · 2019Article
- Inhibition of Mast Cell Function and Proliferation by mTOR Activator MHY1485.Immune network · 2018Article
- Role of mTOR Complexes in Neurogenesis.International journal of molecular sciences · 2018Review
- mTOR Signaling and Neural Stem Cells: The Tuberous Sclerosis Complex Model.International journal of molecular sciences · 2018Review
- Autism spectrum disorder: neuropathology and animal models.Acta neuropathologica · 2017Review
- Dysfunctional mTORC1 Signaling: A Convergent Mechanism between Syndromic and Nonsyndromic Forms of Autism Spectrum Disorder?International journal of molecular sciences · 2017Review
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
- Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the Tsc1 or Tsc2 genes cause tuberous sclerosis complex (TSC). Tsc1 and Tsc2 proteins form a complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) signalling through Rheb-GTPase. We found that Tsc2(+/-) neurons showed impaired spine synapse formation, which was resistant to an mTORC1 inhibitor. Knockdown of mTOR also failed to restore these abnormalities, suggesting mTORC may not participate in impaired spinogenesis in Tsc2(+/-) neurons. To address whether Rheb activation impairs spine synapse formation, we expressed active and inactive forms of Rheb in WT and Tsc2(+/-) neurons, respectively. Expression of active Rheb abolished dendritic spine formation in WT neurons, whereas inactive Rheb restored spine synapse formation in Tsc2(+/-) neurons. Moreover, inactivation of Rheb with farnesyl transferase inhibitors recovered spine synapse morphogenesis in Tsc2(+/-) neurons. In conclusion, dendritic spine abnormalities in TSC neurons may be caused through activation of Rheb, but not through of mTORC1.
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