scholarly journals A coevolved EDS1-SAG101-NRG1 module mediates cell death signaling by TIR-domain immune receptors

2019 ◽  
Author(s):  
Dmitry Lapin ◽  
Viera Kovacova ◽  
Xinhua Sun ◽  
Joram Dongus ◽  
Deepak D. Bhandari ◽  
...  
Keyword(s):  
Cell Death ◽  
Coiled Coil ◽  
Rate Variation ◽  
Distinctive Features ◽  
Tir Domain ◽  
Immune Receptors ◽  
Pathogen Effectors ◽  
Cell Death Signaling ◽  
Basal Defense

AbstractPlant intracellular nucleotide-binding/leucine-rich repeat (NLR) immune receptors are activated by pathogen effectors to trigger host defenses and cell death. Toll-Interleukin1-receptor (TIR)-domain NLRs (TNLs) converge on the Enhanced Disease Susceptibility1 (EDS1) family of lipase-like proteins for all resistance outputs. In Arabidopsis TNL immunity,AtEDS1 heterodimers with Phytoalexin Deficient4 (AtPAD4) transcriptionally boost basal defense pathways.AtEDS1 uses the same surface to interact with PAD4-related Senescence-Associated Gene101 (AtSAG101), but the role ofAtEDS1-AtSAG101 heterodimers was unclear. We show thatAtEDS1-AtSAG101 function together withAtNRG1 coiled-coil domain helper NLRs as a coevolved TNL cell death signaling module.AtEDS1-AtSAG101-AtNRG1 cell death activity is transferable to the solanaceous species,Nicotiana benthamiana, and cannot be substituted byAtEDS1-AtPAD4 withAtNRG1 orAtEDS1-AtSAG101 with endogenousNbNRG1. Analysis of EDS1-family evolutionary rate variation and heterodimer structure-guided phenotyping ofAtEDS1 variants orAtPAD4-AtSAG101 chimeras identify closely aligned α-helical coil surfaces in theAtEDS1-AtSAG101 partner C-terminal domains that are necessary for TNL cell death signaling. Our data suggest that TNL-triggered cell death and pathogen growth restriction are determined by distinctive features of EDS1-SAG101 and EDS1-PAD4 complexes and that these signaling machineries coevolved with further components within plant species or clades to regulate downstream pathways in TNL immunity.

scholarly journals A Coevolved EDS1-SAG101-NRG1 Module Mediates Cell Death Signaling by TIR-Domain Immune Receptors

2019 ◽  
Vol 31 (10) ◽  
pp. 2430-2455 ◽  
Author(s):  
Dmitry Lapin ◽  
Viera Kovacova ◽  
Xinhua Sun ◽  
Joram A. Dongus ◽  
Deepak Bhandari ◽  
...  
Keyword(s):  
Cell Death ◽  
Tir Domain ◽  
Immune Receptors ◽  
Cell Death Signaling

scholarly journals Cytosolic activation of cell death and stem rust resistance by cereal MLA-family CC–NLR proteins

2016 ◽  
Vol 113 (36) ◽  
pp. 10204-10209 ◽  
Author(s):  
Stella Cesari ◽  
John Moore ◽  
Chunhong Chen ◽  
Daryl Webb ◽  
Sambasivam Periyannan ◽  
...  
Keyword(s):  
Cell Death ◽  
Disease Resistance ◽  
Stem Rust ◽  
Nuclear Export ◽  
Rust Resistance ◽  
Stem Rust Resistance ◽  
Full Length ◽  
Induce Cell Death ◽  
Immune Receptors ◽  
Cell Death Signaling

Plants possess intracellular immune receptors designated “nucleotide-binding domain and leucine-rich repeat” (NLR) proteins that translate pathogen-specific recognition into disease-resistance signaling. The wheat immune receptors Sr33 and Sr50 belong to the class of coiled-coil (CC) NLRs. They confer resistance against a broad spectrum of field isolates of Puccinia graminis f. sp. tritici, including the Ug99 lineage, and are homologs of the barley powdery mildew-resistance protein MLA10. Here, we show that, similarly to MLA10, the Sr33 and Sr50 CC domains are sufficient to induce cell death in Nicotiana benthamiana. Autoactive CC domains and full-length Sr33 and Sr50 proteins self-associate in planta. In contrast, truncated CC domains equivalent in size to an MLA10 fragment for which a crystal structure was previously determined fail to induce cell death and do not self-associate. Mutations in the truncated region also abolish self-association and cell-death signaling. Analysis of Sr33 and Sr50 CC domains fused to YFP and either nuclear localization or nuclear export signals in N. benthamiana showed that cell-death induction occurs in the cytosol. In stable transgenic wheat plants, full-length Sr33 proteins targeted to the cytosol provided rust resistance, whereas nuclear-targeted Sr33 was not functional. These data are consistent with CC-mediated induction of both cell-death signaling and stem rust resistance in the cytosolic compartment, whereas previous research had suggested that MLA10-mediated cell-death and disease resistance signaling occur independently, in the cytosol and nucleus, respectively.

scholarly journals Proapoptotic Bad Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish

2021 ◽  
Vol 22 (9) ◽  
pp. 4832
Author(s):  
Jo-Chi Hung ◽  
Jen-Leih Wu ◽  
Jiann-Ruey Hong
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Environmental Stress ◽  
Brain Development ◽  
The Novel ◽  
Germ Layers ◽  
Cell Death Signaling ◽  
Morpholino Oligonucleotides ◽  
Material Factor

The BH3-only molecule Bad regulates cell death via its differential protein phosphorylation, but very few studies address its effect on early embryonic development in vertebrate systems. In this work, we examined the novel role of zebrafish Bad in the initial programmed cell death (PCD) for brain morphogenesis through reducing environmental stress and cell death signaling. Bad was considered to be a material factor that because of the knockdown of Bad by morpholino oligonucleotides, PCD was increased and the reactive oxygen species (ROS) level was enhanced, which correlated to trigger a p53/caspase-8 involving cell death signaling. This Bad knockdown-mediated environmental stress and enhanced cell dying can delay normal cell migration in the formation of the three germ layers, especially the ectoderm, for further brain development. Furthermore, Bad defects involved in three-germ-layers development at 8 hpf were identified by in situ hybridization approach on cyp26, rtla, and Sox17 pattern expression markers. Finally, the Bad knockdown-induced severely defected brain was examined by tissue section from 24 to 48 h postfertilization (hpf), which correlated to induce dramatic malformation in the hindbrain. Our data suggest that the BH3-only molecule Bad regulates brain development via controlling programmed cell death on overcoming environmental stress for reducing secondary cell death signaling, which suggests that correlates to brain developmental and neurological disorders in this model system.

scholarly journals Dual Regulatory Roles of the Extended N Terminus for Activation of the Tomato Mi-1.2 Resistance Protein

2012 ◽  
Vol 25 (8) ◽  
pp. 1045-1057 ◽  
Author(s):  
Ewa Lukasik-Shreepaathy ◽  
Erik Slootweg ◽  
Hanna Richter ◽  
Aska Goverse ◽  
Ben J. C. Cornelissen ◽  
...  
Keyword(s):  
Cell Death ◽  
Coiled Coil ◽  
Terminal Region ◽  
Regulatory Function ◽  
Cell Death Response ◽  
N Terminus ◽  
Positive Regulators ◽  
In Trans ◽  
Lrr Protein

Plant resistance (R) proteins mediate race-specific immunity and initiate host defenses that are often accompanied by a localized cell-death response. Most R proteins belong to the nucleotide binding-leucine-rich repeat (NB-LRR) protein family, as they carry a central NB-ARC domain fused to an LRR domain. The coiled-coil (CC) domain at the N terminus of some solanaceous NB-LRR proteins is extended with a solanaceae domain (SD). Tomato Mi-1.2, which confers resistance against nematodes, white flies, psyllids, and aphids, encodes a typical SD-CNL protein. Here, we analyzed the role of the extended N terminus for Mi-1.2 activation. Removal of the first part of the N terminus (Nt1) induced Mi-1.2-mediated cell death that could be suppressed by overexpression of the second half of the N-terminal region. Yet, autoactivating NB-ARC-LRR mutants require in trans coexpression of the N-terminal region to induce cell death, indicating that the N terminus functions both as a negative and as a positive regulator. Based on secondary structure predictions, we could link both activities to three distinct subdomains, a typical CC domain and two novel, structurally-conserved helical subdomains called SD1 and SD2. A negative regulatory function could be assigned to the SD1, whereas SD2 and the CC together function as positive regulators of Mi-1.2-mediated cell death.

scholarly journals Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nan Yang ◽  
Qi-Wen Guan ◽  
Fang-Hui Chen ◽  
Qin-Xuan Xia ◽  
Xi-Xi Yin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Brain Activity ◽  
Related Factor ◽  
Mitochondrial Oxidative Stress ◽  
Electrical Brain Activity ◽  
Neuroprotective Strategies ◽  
Cell Death Signaling ◽  
Stress Oxidative

Mitochondria are major sources of reactive oxygen species (ROS) within the cell and are especially vulnerable to oxidative stress. Oxidative damage to mitochondria results in disrupted mitochondrial function and cell death signaling, finally triggering diverse pathologies such as epilepsy, a common neurological disease characterized with aberrant electrical brain activity. Antioxidants are considered as promising neuroprotective strategies for epileptic condition via combating the deleterious effects of excessive ROS production in mitochondria. In this review, we provide a brief discussion of the role of mitochondrial oxidative stress in the pathophysiology of epilepsy and evidences that support neuroprotective roles of antioxidants targeting mitochondrial oxidative stress including mitochondria-targeted antioxidants, polyphenols, vitamins, thiols, and nuclear factor E2-related factor 2 (Nrf2) activators in epilepsy. We point out these antioxidative compounds as effectively protective approaches for improving prognosis. In addition, we specially propose that these antioxidants exert neuroprotection against epileptic impairment possibly by modulating cell death interactions, notably autophagy-apoptosis, and autophagy-ferroptosis crosstalk.

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