The Experts below are selected from a list of 424155 Experts worldwide ranked by ideXlab platform
Jiři Friml - One of the best experts on this subject based on the ideXlab platform.
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tir1 afb aux iaa auxin perception mediates rapid cell wall Acidification and Growth of arabidopsis hypocotyls
eLife, 2016Co-Authors: Matyas Fendrych, Jeffrey Leung, Jiři FrimlAbstract:Despite being composed of immobile cells, plants reorient along directional stimuli. The hormone auxin is redistributed in stimulated organs leading to differential Growth and bending. Auxin application triggers rapid cell wall Acidification and elongation of aerial organs of plants, but the molecular players mediating these effects are still controversial. Here we use genetically-encoded pH and auxin signaling sensors, pharmacological and genetic manipulations available for Arabidopsis etiolated hypocotyls to clarify how auxin is perceived and the downstream Growth executed. We show that auxin-induced Acidification occurs by local activation of H+-ATPases, which in the context of gravity response is restricted to the lower organ side. This auxin-stimulated Acidification and Growth require TIR1/AFB-Aux/IAA nuclear auxin perception. In addition, auxin-induced gene transcription and specifically SAUR proteins are crucial downstream mediators of this Growth. Our study provides strong experimental support for the Acid Growth theory and clarified the contribution of the upstream auxin perception mechanisms.
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TIR1/AFB-Aux/IAA auxin perception mediates rapid cell wall Acidification and Growth of Arabidopsis hypocotyls
eLife, 2016Co-Authors: Matyas Fendrych, Jeffrey Leung, Jiři FrimlAbstract:Despite being composed of immobile cells, plants reorient along directional stimuli. The hormone auxin is redistributed in stimulated organs leading to differential Growth and bending. Auxin application triggers rapid cell wall Acidification and elongation of aerial organs of plants, but the molecular players mediating these effects are still controversial. Here we use genetically-encoded pH and auxin signaling sensors, pharmacological and genetic manipulations available for Arabidopsis etiolated hypocotyls to clarify how auxin is perceived and the downstream Growth executed. We show that auxin-induced Acidification occurs by local activation of H+-ATPases, which in the context of gravity response is restricted to the lower organ side. This auxin-stimulated Acidification and Growth require TIR1/AFB-Aux/IAA nuclear auxin perception. In addition, auxin-induced gene transcription and specifically SAUR proteins are crucial downstream mediators of this Growth. Our study provides strong experimental support for the Acid Growth theory and clarified the contribution of the upstream auxin perception mechanisms.
Robert B. Abramovitch - One of the best experts on this subject based on the ideXlab platform.
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Remodeling of Mycobacterium tuberculosis lipids regulates prpCD during Acid Growth arrest
2019Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Abstract Mycobacterium tuberculosis (Mtb) establishes a state of non-replicating persistence when it is cultured at Acidic pH with glycerol as a sole carbon source. Growth can be restored by spontaneous mutations in the ppe51 gene or supplementation with pyruvate, supporting that Acid Growth arrests is a genetically controlled, adaptive process and not simply a physiological limitation associated with Acidic pH. Transcriptional profiling identified the methylcitrate synthase and methylcitrate dehydratase genes (prpC and prpD, respectively) as being selectively induced during Acid Growth arrest. prpCD along with isocitrate lyase (icl) enable Mtb to detoxify propionyl-CoA through the methylcitrate cycle. The goal of this study was to examine mechanisms underlying the regulation of prpCD during Acid Growth arrest. Induction of prpCD during Acid Growth arrest was reduced when the medium was supplemented with vitamin B12 (which enables an alternative propionate detoxification pathway) and enhanced in an icl mutant (which is required for the propionate detoxification), suggesting that Mtb is responding to elevated levels of propionyl-CoA during Acidic Growth arrest. We hypothesized that an endogenous source of propionyl-CoA generated during metabolism of methyl-branched lipids may be regulating prpCD. Using Mtb radiolabeled with 14C-propionate or 14C-acetate, it was observed that lipids are remodeled during Acid Growth arrest, with triacylglycerol being catabolized and sulfolipid and trehalose dimycolate being synthesized. Blocking TAG lipolysis using the lipase inhibitor tetrahydrolipstatin, resulted in enhanced prpC induction during Acid Growth arrest, suggesting that lipid remodeling may function, in part, to detoxify propionate. Notably, prpC was not induced during Acid Growth arrest when using lactate instead of glycerol. We propose that metabolism of glycerol at Acidic pH may result in the accumulation of propionyl-CoA and that lipid remodeling may function as a detoxification mechanism. Importance During infection, Mycobacterium tuberculosis (Mtb) colonizes Acidic environments, such as the macrophage phagosome and granuloma. Understanding regulatory and metabolic adaptations that occur in response to Acidic pH can provide insights int0 mechanisms used by the bacterium to adapt to the host. We have previously shown that Mtb exhibits pH-dependent metabolic adaptations and requires anaplerotic enzymes, such as Icl1/2 and PckA, to grow optimally at Acidic pH. Additionally, we have observed that Mtb can only grow on specific carbon sources at Acidic pH. Together these findings show that Mtb integrates environmental pH and carbon source to regulate its metabolism. In this study, it is shown that Mtb remodels its lipids and modulates the expression of propionyl-CoA detoxifying genes prpCD when grown on glycerol at Acidic pH. This finding suggests that lipid remodeling at Acidic pH may contribute to detoxification of propionyl-CoA, by incorporating the metabolite into methyl-branched cell envelope lipids.
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Genetic and metabolic regulation of Mycobacterium tuberculosis Acid Growth arrest.
Scientific reports, 2018Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Mycobacterium tuberculosis (Mtb) senses and adapts to Acidic environments during the course of infection. Acidic pH-dependent adaptations include the induction of metabolic genes associated with anaplerosis and Growth arrest on specific carbon sources. Here we report that deletion of isocitrate lyase or phosphoenolpyruvate carboxykinase results in reduced Growth at Acidic pH and altered metabolite profiles, supporting that remodeling of anaplerotic metabolism is required for pH-dependent adaptation. Mtb cultured at pH 5.7 in minimal medium containing glycerol as a single carbon source exhibits an Acid Growth arrest phenotype, where the bacterium is non-replicating but viable and metabolically active. The bacterium assimilates and metabolizes glycerol and maintains ATP pools during Acid Growth arrest and becomes tolerant to detergent stress and the antibiotics isoniazid and rifampin. A forward genetic screen identified mutants that do not arrest their Growth at Acidic pH, including four enhanced Acid Growth (eag) mutants with three distinct mutations in the proline-proline-glutamate (PPE) gene MT3221 (also named ppe51). Overexpression of the MT3221(S211R) variant protein in wild type Mtb results in enhanced Acid Growth and reduced drug tolerance. These findings support that Acid Growth arrest is a genetically controlled, adaptive process and not simply a physiological limitation associated with Acidic pH.
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Genetic and metabolic regulation of Mycobacterium tuberculosis Acid Growth arrest
2017Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Mycobacterium tuberculosis (Mtb) senses and adapts to Acidic environments during the course of infection. Acidic pH-dependent adaptations include the induction of metabolic genes associated with anaplerosis and Growth arrest on specific carbon sources. In this study, reverse and forward genetic studies were undertaken to define new mechanisms underlying pH-dependent adaptations. Here we report that deletion of isocitrate lyase ( icl1/2 ) or phosphoenolpyruvate carboxykinase ( pckA ) results in reduced Growth at Acidic pH and altered metabolite profiles, supporting that remodeling of anaplerotic metabolism is required for pH-dependent adaptation. Mtb cultured at pH 5.7 in minimal medium containing glycerol as a single carbon source exhibits an Acid Growth arrest phenotype, where the bacterium is non-replicating but viable and metabolically active. The bacterium uptakes and metabolizes glycerol and maintains ATP pools during Acid Growth arrest and becomes tolerant to detergent stress and the antibiotics isoniazid and rifampin. A forward genetic screen identified mutants that do not arrest their Growth at Acidic pH, including four enhanced Acid Growth ( eag ) mutants with three distinct mutations in the PPE gene MT3221. Overexpression of the MT3221(S211R) variant protein in wild type Mtb results in enhanced Acid Growth and reduced drug tolerance. Together, these findings provide new evidence for a genetic and physiological basis for Acid Growth arrest and support that Growth arrest is an adaptive process and not simply a physiological limitation associated with Acidic pH.
Yasuomi Tada - One of the best experts on this subject based on the ideXlab platform.
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chemical hijacking of auxin signaling with an engineered auxin tir1 pair
Nature Chemical Biology, 2018Co-Authors: Naoyuki Uchida, Koji Takahashi, Rie Iwasaki, Ryotaro Yamada, Masahiko Yoshimura, Takaho A Endo, Seisuke Kimura, Hua Zhang, Mika Nomoto, Yasuomi TadaAbstract:A synthetic, orthogonal pair of the plant hormone auxin and its receptor TIR1 was engineered to hijack auxin signaling without interfering with the endogenous system. The synthetic system conclusively demonstrates the role for TIR1 in auxin-induced Acid Growth. The phytohormone auxin indole-3-acetic Acid (IAA) regulates nearly all aspects of plant Growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-box proteins. Here we report an engineered, orthogonal auxin–TIR1 receptor pair, developed through a bump-and-hole strategy, that triggers auxin signaling without interfering with endogenous auxin or TIR1/AFBs. A synthetic, convex IAA (cvxIAA) hijacked the downstream auxin signaling in vivo both at the transcriptomic level and in specific developmental contexts, only in the presence of a complementary, concave TIR1 (ccvTIR1) receptor. Harnessing the cvxIAA–ccvTIR1 system, we provide conclusive evidence for the role of the TIR1-mediated pathway in auxin-induced seedling Acid Growth. The cvxIAA–ccvTIR1 system serves as a powerful tool for solving outstanding questions in auxin biology and for precise manipulation of auxin-mediated processes as a controllable switch.
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Chemical hijacking of auxin signaling with an engineered auxin-TIR1 pair.
Nature chemical biology, 2018Co-Authors: Naoyuki Uchida, Koji Takahashi, Rie Iwasaki, Ryotaro Yamada, Masahiko Yoshimura, Takaho A Endo, Seisuke Kimura, Hua Zhang, Mika Nomoto, Yasuomi TadaAbstract:The phytohormone auxin indole-3-acetic Acid (IAA) regulates nearly all aspects of plant Growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-box proteins. Here we report an engineered, orthogonal auxin-TIR1 receptor pair, developed through a bump-and-hole strategy, that triggers auxin signaling without interfering with endogenous auxin or TIR1/AFBs. A synthetic, convex IAA (cvxIAA) hijacked the downstream auxin signaling in vivo both at the transcriptomic level and in specific developmental contexts, only in the presence of a complementary, concave TIR1 (ccvTIR1) receptor. Harnessing the cvxIAA-ccvTIR1 system, we provide conclusive evidence for the role of the TIR1-mediated pathway in auxin-induced seedling Acid Growth. The cvxIAA-ccvTIR1 system serves as a powerful tool for solving outstanding questions in auxin biology and for precise manipulation of auxin-mediated processes as a controllable switch.
Matyas Fendrych - One of the best experts on this subject based on the ideXlab platform.
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tir1 afb aux iaa auxin perception mediates rapid cell wall Acidification and Growth of arabidopsis hypocotyls
eLife, 2016Co-Authors: Matyas Fendrych, Jeffrey Leung, Jiři FrimlAbstract:Despite being composed of immobile cells, plants reorient along directional stimuli. The hormone auxin is redistributed in stimulated organs leading to differential Growth and bending. Auxin application triggers rapid cell wall Acidification and elongation of aerial organs of plants, but the molecular players mediating these effects are still controversial. Here we use genetically-encoded pH and auxin signaling sensors, pharmacological and genetic manipulations available for Arabidopsis etiolated hypocotyls to clarify how auxin is perceived and the downstream Growth executed. We show that auxin-induced Acidification occurs by local activation of H+-ATPases, which in the context of gravity response is restricted to the lower organ side. This auxin-stimulated Acidification and Growth require TIR1/AFB-Aux/IAA nuclear auxin perception. In addition, auxin-induced gene transcription and specifically SAUR proteins are crucial downstream mediators of this Growth. Our study provides strong experimental support for the Acid Growth theory and clarified the contribution of the upstream auxin perception mechanisms.
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TIR1/AFB-Aux/IAA auxin perception mediates rapid cell wall Acidification and Growth of Arabidopsis hypocotyls
eLife, 2016Co-Authors: Matyas Fendrych, Jeffrey Leung, Jiři FrimlAbstract:Despite being composed of immobile cells, plants reorient along directional stimuli. The hormone auxin is redistributed in stimulated organs leading to differential Growth and bending. Auxin application triggers rapid cell wall Acidification and elongation of aerial organs of plants, but the molecular players mediating these effects are still controversial. Here we use genetically-encoded pH and auxin signaling sensors, pharmacological and genetic manipulations available for Arabidopsis etiolated hypocotyls to clarify how auxin is perceived and the downstream Growth executed. We show that auxin-induced Acidification occurs by local activation of H+-ATPases, which in the context of gravity response is restricted to the lower organ side. This auxin-stimulated Acidification and Growth require TIR1/AFB-Aux/IAA nuclear auxin perception. In addition, auxin-induced gene transcription and specifically SAUR proteins are crucial downstream mediators of this Growth. Our study provides strong experimental support for the Acid Growth theory and clarified the contribution of the upstream auxin perception mechanisms.
Jacob J. Baker - One of the best experts on this subject based on the ideXlab platform.
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Remodeling of Mycobacterium tuberculosis lipids regulates prpCD during Acid Growth arrest
2019Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Abstract Mycobacterium tuberculosis (Mtb) establishes a state of non-replicating persistence when it is cultured at Acidic pH with glycerol as a sole carbon source. Growth can be restored by spontaneous mutations in the ppe51 gene or supplementation with pyruvate, supporting that Acid Growth arrests is a genetically controlled, adaptive process and not simply a physiological limitation associated with Acidic pH. Transcriptional profiling identified the methylcitrate synthase and methylcitrate dehydratase genes (prpC and prpD, respectively) as being selectively induced during Acid Growth arrest. prpCD along with isocitrate lyase (icl) enable Mtb to detoxify propionyl-CoA through the methylcitrate cycle. The goal of this study was to examine mechanisms underlying the regulation of prpCD during Acid Growth arrest. Induction of prpCD during Acid Growth arrest was reduced when the medium was supplemented with vitamin B12 (which enables an alternative propionate detoxification pathway) and enhanced in an icl mutant (which is required for the propionate detoxification), suggesting that Mtb is responding to elevated levels of propionyl-CoA during Acidic Growth arrest. We hypothesized that an endogenous source of propionyl-CoA generated during metabolism of methyl-branched lipids may be regulating prpCD. Using Mtb radiolabeled with 14C-propionate or 14C-acetate, it was observed that lipids are remodeled during Acid Growth arrest, with triacylglycerol being catabolized and sulfolipid and trehalose dimycolate being synthesized. Blocking TAG lipolysis using the lipase inhibitor tetrahydrolipstatin, resulted in enhanced prpC induction during Acid Growth arrest, suggesting that lipid remodeling may function, in part, to detoxify propionate. Notably, prpC was not induced during Acid Growth arrest when using lactate instead of glycerol. We propose that metabolism of glycerol at Acidic pH may result in the accumulation of propionyl-CoA and that lipid remodeling may function as a detoxification mechanism. Importance During infection, Mycobacterium tuberculosis (Mtb) colonizes Acidic environments, such as the macrophage phagosome and granuloma. Understanding regulatory and metabolic adaptations that occur in response to Acidic pH can provide insights int0 mechanisms used by the bacterium to adapt to the host. We have previously shown that Mtb exhibits pH-dependent metabolic adaptations and requires anaplerotic enzymes, such as Icl1/2 and PckA, to grow optimally at Acidic pH. Additionally, we have observed that Mtb can only grow on specific carbon sources at Acidic pH. Together these findings show that Mtb integrates environmental pH and carbon source to regulate its metabolism. In this study, it is shown that Mtb remodels its lipids and modulates the expression of propionyl-CoA detoxifying genes prpCD when grown on glycerol at Acidic pH. This finding suggests that lipid remodeling at Acidic pH may contribute to detoxification of propionyl-CoA, by incorporating the metabolite into methyl-branched cell envelope lipids.
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Genetic and metabolic regulation of Mycobacterium tuberculosis Acid Growth arrest.
Scientific reports, 2018Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Mycobacterium tuberculosis (Mtb) senses and adapts to Acidic environments during the course of infection. Acidic pH-dependent adaptations include the induction of metabolic genes associated with anaplerosis and Growth arrest on specific carbon sources. Here we report that deletion of isocitrate lyase or phosphoenolpyruvate carboxykinase results in reduced Growth at Acidic pH and altered metabolite profiles, supporting that remodeling of anaplerotic metabolism is required for pH-dependent adaptation. Mtb cultured at pH 5.7 in minimal medium containing glycerol as a single carbon source exhibits an Acid Growth arrest phenotype, where the bacterium is non-replicating but viable and metabolically active. The bacterium assimilates and metabolizes glycerol and maintains ATP pools during Acid Growth arrest and becomes tolerant to detergent stress and the antibiotics isoniazid and rifampin. A forward genetic screen identified mutants that do not arrest their Growth at Acidic pH, including four enhanced Acid Growth (eag) mutants with three distinct mutations in the proline-proline-glutamate (PPE) gene MT3221 (also named ppe51). Overexpression of the MT3221(S211R) variant protein in wild type Mtb results in enhanced Acid Growth and reduced drug tolerance. These findings support that Acid Growth arrest is a genetically controlled, adaptive process and not simply a physiological limitation associated with Acidic pH.
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Genetic and metabolic regulation of Mycobacterium tuberculosis Acid Growth arrest
2017Co-Authors: Jacob J. Baker, Robert B. AbramovitchAbstract:Mycobacterium tuberculosis (Mtb) senses and adapts to Acidic environments during the course of infection. Acidic pH-dependent adaptations include the induction of metabolic genes associated with anaplerosis and Growth arrest on specific carbon sources. In this study, reverse and forward genetic studies were undertaken to define new mechanisms underlying pH-dependent adaptations. Here we report that deletion of isocitrate lyase ( icl1/2 ) or phosphoenolpyruvate carboxykinase ( pckA ) results in reduced Growth at Acidic pH and altered metabolite profiles, supporting that remodeling of anaplerotic metabolism is required for pH-dependent adaptation. Mtb cultured at pH 5.7 in minimal medium containing glycerol as a single carbon source exhibits an Acid Growth arrest phenotype, where the bacterium is non-replicating but viable and metabolically active. The bacterium uptakes and metabolizes glycerol and maintains ATP pools during Acid Growth arrest and becomes tolerant to detergent stress and the antibiotics isoniazid and rifampin. A forward genetic screen identified mutants that do not arrest their Growth at Acidic pH, including four enhanced Acid Growth ( eag ) mutants with three distinct mutations in the PPE gene MT3221. Overexpression of the MT3221(S211R) variant protein in wild type Mtb results in enhanced Acid Growth and reduced drug tolerance. Together, these findings provide new evidence for a genetic and physiological basis for Acid Growth arrest and support that Growth arrest is an adaptive process and not simply a physiological limitation associated with Acidic pH.
