Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration

Esteban-Collado, José; Corominas, Montserrat; Serras, Florenci

doi:10.1242/dev.197087

Cited by 11 publications

(13 citation statements)

References 41 publications

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“…PI3K/Akt signaling is necessary for Ask1 to phosphorylate p38, and the phosphorylation of p38 during regeneration is nutrient sensitive. This finding distinguishes p38 and JNK function in the cells involved in tissue repair and regenerative growth (Esteban-Collado et al 2021 ), but the interaction between JNK and p38 is still elusive. As mentioned above, studies on the roles of JNK and p38 in insect regeneration have mainly focused on Drosophila imaginal discs; the functions of these proteins in other insect appendages are less clear.…”

Section: Internal Mechanisms Underlying Regenerationmentioning

confidence: 98%

“…JNK and p38 are conserved subfamilies of mitogen-activated protein kinases (MAPKs) that sense and elicit cellular responses to stress and tissue damage (Roux and Blenis 2004 ). During wing disc regeneration, apoptotic signal-regulating kinase 1 (Ask1) and Akt kinase (Akt) sense ROS in both dying and living cells to activate moderate phosphorylation levels of p38 and JNK (Esteban-Collado et al 2021 ; Santabárbara-Ruiz et al 2019 ). Damage-induced JNK signaling leads to the upregulation of the Duox-maturation factor NIP, which in turn promotes ROS generation in regenerating tissue (Khan et al 2017 ).…”

Section: Internal Mechanisms Underlying Regenerationmentioning

confidence: 99%

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Physiological and molecular mechanisms of insect appendage regeneration

et al. 2023

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Regeneration, as a fascinating scientific field, refers to the ability of animals replacing lost tissue or body parts. Many metazoan organisms have been reported with the regeneration phenomena, but showing evolutionarily variable abilities. As the most diverse metazoan taxon, hundreds of insects show strong appendage regeneration ability. The regeneration process and ability are dependent on many factors, including macroscopic physiological conditions and microscopic molecular mechanisms. This article reviews research progress on the physiological conditions and internal underlying mechanisms controlling appendage regeneration in insects.

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Section: Internal Mechanisms Underlying Regenerationmentioning

confidence: 98%

Section: Internal Mechanisms Underlying Regenerationmentioning

confidence: 99%

Physiological and molecular mechanisms of insect appendage regeneration

et al. 2023

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“…Thus, it is conceivable that the mechanisms that sense the nutritional status of the organism are key in sensing damage and therefore in the onset of regeneration. Indeed, it has recently been found that nutrient restriction blocks regeneration in similar phenotypes such as downregulation of Pi3K/Akt or in the mutated Ser83 of Ask1 ( Santabárbara-Ruiz et al, 2019 ; Esteban-Collado et al, 2021 ). More importantly, it has also been found that the anomalous regeneration resulting from nutrient restriction or from mutated Ask1 Ser83 can be rescued by ectopic activation of p38, but not of JNK ( Esteban-Collado et al, 2021 ).…”

Section: How Is Damage Sensed?mentioning

confidence: 99%

“…Indeed, it has recently been found that nutrient restriction blocks regeneration in similar phenotypes such as downregulation of Pi3K/Akt or in the mutated Ser83 of Ask1 ( Santabárbara-Ruiz et al, 2019 ; Esteban-Collado et al, 2021 ). More importantly, it has also been found that the anomalous regeneration resulting from nutrient restriction or from mutated Ask1 Ser83 can be rescued by ectopic activation of p38, but not of JNK ( Esteban-Collado et al, 2021 ). These observations demonstrate that the function of Pi3K/Akt in regeneration is channelled through p38 rather than JNK.…”

Section: How Is Damage Sensed?mentioning

confidence: 99%

The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in Drosophila

Serras

2022

Front. Cell Dev. Biol.

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One of the main topics in regeneration biology is the nature of the early signals that trigger the damage response. Recent advances in Drosophila point to the MAP3 kinase Ask1 as a molecular hub that integrates several signals at the onset of regeneration. It has been discovered that reactive oxygen species (ROS) produced in damaged imaginal discs and gut epithelia will activate the MAP3 kinase Ask1. Severely damaged and apoptotic cells produce an enormous amount of ROS, which ensures their elimination by activating Ask1 and in turn the pro-apoptotic function of JNK. However, this creates an oxidative stress environment with beneficial effects that is sensed by neighboring healthy cells. This environment, in addition to the Pi3K/Akt nutrient sensing pathway, can be integrated into Ask1 to launch regeneration. Ultimately the activity of Ask1 depends on these and other inputs and modulates its signaling to achieve moderate levels of p38 and low JNK signaling and thus promote survival and regeneration. This model based on the dual function of Ask1 for early response to damage is discussed here.

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“…In Drosophila , Ask1 in the gut and imaginal epithelia operates as a survival signal in tissue regeneration by triggering a non-apoptotic function of p38 (Patel et al, 2019; Santabárbara-Ruiz et al, 2019). This is achieved by a ROS-dependent, Akt-induced phosphorylation of Ser83 in Ask1 (Ser174 in humans) that is essential to redirect the Ask1 signaling pathway towards p38 and thus drive regeneration (Esteban-Collado et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

ROS-mediated TNFR Wengen activation in response to apoptosis

Esteban-Collado,

Fernàndez-Mañas,

Fernández-Moreno

et al. 2023

Preprint

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The activation of tumor necrosis factor receptors (TNFR) controls pleiotropic pro-inflammatory functions ranging from apoptosis to survival. The ability to trigger a particular function will depend on the upstream activation, association with regulatory complexes and downstream pathways. InDrosophila,two TNFRs have been identified, Wengen (Wgn) and Grindelwald (Grnd). Although several reports associate these receptors with JNK-dependent apoptosis, it has recently been found that Wgn activates a variety of functions. We demonstrate that Wgn is required for survival by protecting cells from apoptosis. This is mediated by the signaling molecule dTRAF1 and results in the activation of the p38 MAP kinase signaling pathway. Remarkably, Wgn is required for apoptosis-induced regeneration and is activated by the reactive oxygen species (ROS) produced following apoptosis. This ROS activation is exclusive for Wgn, but not for Grnd, and occurs in the absence of the ligand Eiger/TNFα. Furthermore, based on protein sequence conservation, the extracellular Cys-rich domain of Grnd is much more divergent and phylogenetically restricted than that of Wgn, which is more similar to TNFR families from other animals, including those of human TNFRs. Taken together, our results show a novel function for a TNFR that responds to cellular damage by ensuring the cell survival required for the response to damage.

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Nutrition and PI3K/Akt signaling are required for p38-dependent regeneration

Cited by 11 publications

References 41 publications

Physiological and molecular mechanisms of insect appendage regeneration

Physiological and molecular mechanisms of insect appendage regeneration

The sooner, the better: ROS, kinases and nutrients at the onset of the damage response in Drosophila

ROS-mediated TNFR Wengen activation in response to apoptosis

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