Tuberous sclerosis complex regulates Drosophila neuromuscular junction growth via the TORC2/Akt pathway

Natarajan, Rajalaxmi; Trivedi, Deepti; Wairkar, Yogesh P.

doi:10.1093/hmg/ddt053

Cited by 36 publications

(45 citation statements)

References 65 publications

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“…According to Dimitroff et al (2012), these findings demonstrate that different inputs to InR/TOR signaling have specific activities in the nervous system development, and that Tor provides a connection between nutrient-energy sensing systems and patterning of the nervous system. The role of TPRC2 in regulating proper synaptic growth was further confirmed by (Natarajan et al 2013). Gigas and Rictor mutants show increased synaptic growth, whereas Raptor knockdown has no effect on this trait.…”

Section: Inr/tor Pathwaymentioning

confidence: 84%

Neuronal Genes and Developmental Neuronal Pathways in Drosophila Life Span Control

Pasyukova

Symonenko

Roshina

et al. 2015

Healthy Ageing and Longevity

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The nervous system has long been suggested as a key tissue that defines life span. The identity of neuronal cell types is established during development and maintained throughout adulthood due to the expression of specific neuronal genes coding for ion channels, neurotransmitters and neuropeptides, G-protein-coupled receptors, motor proteins, recognition and adhesion molecules. In this paper, we review data on the role of neuronal genes in Drosophila melanogaster life span control. Several pathways responsible for life span regulation are also important for the development of the nervous system. Genes involved in insulin-like, Target of Rapamycin, Janus Kinase/Signal Transducer and Activator of Transcription and cell polarity pathways, a number of global regulators and transcription factors play key roles both in aging and longevity control and in shaping the nervous system as a network of specialized neuronal cells in early development. Is their impact on life span related, at least partially, to their developmental functions or is it explained by other pleiotropic influences later in life? In this paper, we address this question based on the published data and our own findings.

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Section: Inr/tor Pathwaymentioning

confidence: 84%

Neuronal Genes and Developmental Neuronal Pathways in Drosophila Life Span Control

Pasyukova

Symonenko

Roshina

et al. 2015

Healthy Ageing and Longevity

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“…Drosophila neuromuscular junction (NMJ) was used to determine the role of TSC complex-Rheb-mTORC1 signaling on synapse assembly and function (Knox et al, 2007;Dimitroff et al, 2012;Natarajan et al, 2013). S6K regulated overall synapse growth (synapse bouton size, active zone number, and density) but not synaptic enlargement measured by the number of synaptic boutons per muscle area (Cheng et al, 2011a).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

“…Recent findings show that Rheb over-expression mediated synaptic growth was morphologically and functionally different from that of the TSC mutant, indicating that TSC complex may be able to regulate NMJ synapse independent of Rheb-TORC1 pathway (Natarajan et al, 2013). TSC2 was known to regulate actin cytoskeleton through TORC2, which is critical for NMJ growth and function (Eaton et al, 2002;Luo 2002;Loewith et al, 2002;Coyle et al, 2004;Jacinto et al, 2004;Natarajan et al, 2013).…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

“…TSC2 was known to regulate actin cytoskeleton through TORC2, which is critical for NMJ growth and function (Eaton et al, 2002;Luo 2002;Loewith et al, 2002;Coyle et al, 2004;Jacinto et al, 2004;Natarajan et al, 2013). Detailed studies on synaptic growth and enlargement were not yet reported in mice and more investigations in mammals into the role of Rheb and mTORC2 (Yang et al, 2006) would help to understand the regulation of brain connectivity.…”

Section: Rheb In Synapse Size and Functionmentioning

confidence: 99%

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Rheb in neuronal degeneration, regeneration, and connectivity

Potheraveedu

Schöpel

Stoll

et al. 2017

Biological Chemistry

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Abstract:The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake. The subcellular localization of Rheb and its interacting proteins critically regulate its activity and function. In stem cells, constitutive activation of Rheb enhances differentiation at the expense of self-renewal partially explaining the adverse effects of deregulated Rheb in the mammalian brain. In the context of various cellular stress conditions such as oxidative stress, ER-stress, death factor signaling, and cellular aging, Rheb activation surprisingly enhances rather than prevents cellular degeneration. This review addresses cell type-and cell state-specific function(s) of Rheb and mainly focuses on neurons and their surrounding glial cells. Mechanisms will be discussed in the context of therapy that interferes with Rheb's activity using the antibiotic rapamycin or low molecular weight compounds.

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“…TOR proteins are best known for roles in the nutrient-dependent signaling pathways underlying cell growth, proliferation, and survival (Weisman et al, 2014). TOR genes, which have been isolated in all eukaryotes investigated, form two functionally distinct complexes, TORC1 (CRTC1) and TORC2 (CRTC2); both have been the focus of metabolic and cancer studies for many years (Wullschleger et al, 2006;Loewith and Hall, 2011;Natarajan et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Association of CRTC2 gene polymorphisms with growth and meat quality traits of Qinchuan cattle

Xu¹,

Gui²,

Song³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Growth and meat quality traits play important roles in the evaluation of cattle productivity and are influenced by genetic and environmental factors. CRTC2 is a recently discovered gene related to obesity that may influence fat deposition. The aim of the current study was to detect polymorphisms of bovine CRTC2 and explore their relationships to growth and meat quality in Qinchuan cattle. Three single nucleotide polymorphisms (SNPs); g.3001 C>T; g.3034 G>A; and g.3467 T>C, were identified from sequencing results of 422 Qinchuan cattle. The genotypic distributions of both g.3034 G>A and g.3467 T>C mutations were in agreement with Hardy-Weinberg equilibrium, (P < 0.05), while the T3001C mutation was not (P > 0.05), based on χ 2 test analysis. The SNPs g.3001 C>T and g.3034 G>A are missense mutations (Ser/Phe and Ser/ 12913 SNPs in bovine CRTC2 and economic production traits ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 12912-12920 (2015) Thr respectively). Additionally, SNPs g.3034 G>A and g.3467 T>C showed a medium polymorphism level (0.25 < PIC< 0.50), whereas g.3001 C>T showed a low polymorphism level (PIC < 0.25). These three SNPs were significantly associated with several growth and meat quality traits in the Qinchuan cattle population (P < 0.05 or P < 0.01). Collectively, these results demonstrate that CRTC2 is involved in the regulation of cattle growth and meat quality, and suggest that CRTC2 is a potential candidate gene for marker-assisted selection in future breeding development programs for Qinchuan cattle.

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Tuberous sclerosis complex regulates Drosophila neuromuscular junction growth via the TORC2/Akt pathway

Cited by 36 publications

References 65 publications

Neuronal Genes and Developmental Neuronal Pathways in Drosophila Life Span Control

Neuronal Genes and Developmental Neuronal Pathways in Drosophila Life Span Control

Rheb in neuronal degeneration, regeneration, and connectivity

Association of CRTC2 gene polymorphisms with growth and meat quality traits of Qinchuan cattle

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