scholarly journals The TIR-NBS-LRR protein CSA1 is required for autoimmune cell death in Arabidopsis pattern recognition co-receptor bak1 and bir3 mutants

2021 ◽  
Author(s):  
Sarina Schulze ◽  
Liping Yu ◽  
Alexandra Ehinger ◽  
Dagmar Kolb ◽  
Svenja Saile ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pattern Recognition ◽  
Cell Death ◽  
Double Mutant ◽  
Direct Interaction ◽  
Shade Avoidance ◽  
Receptor Kinase ◽  
Effector Triggered Immunity ◽  
Lrr Protein ◽  
Spontaneous Cell Death

The BRI1-associated kinase BAK1/SERK3 is a positive regulator of multiple leucine rich receptor kinase-mediated signaling pathways including pattern triggered immunity (PTI). Absence or overexpression of BAK1 leads to spontaneous cell death formation. BAK1-interacting receptors (BIR) constitutively interact with BAK1, and plants lacking or overexpressing BIR proteins phenocopy the cell death symptoms observed in bak1 knock outs or overexpressors. In the interactome of BIR3, the TIR-NBS-LRR protein CONSTITUTIVE SHADE-AVOIDANCE 1 (CSA1) was identified by mass spectrometry. CSA1 physically interacts with BIR proteins and can be detected in complexes with BAK1. Direct interaction was shown only for CSA1 with BIR proteins but not BAK1. Double mutant bak1 bir3 genotypes develop strong dwarfism and cell death symptoms that are dependent on EDS1 and salicylic acid. Loss of CSA1 blocks bak1 and bak1 bir3-mediated cell death formation thus demonstrating that CSA1 is causal for this type of cell death. We propose that CSA1 guards BIR proteins and initiates autoimmune cell death that is observed when BAK1 BIR complexes are impaired. Our findings reveal how cell death in the absence of BAK1 and BIR3 is executed and links BAK1, a common co-receptor of many pattern recognition receptors, to NLR proteins typically implicated in effector-triggered immunity.

scholarly journals Overexpression of Pto Induces a Salicylate-Independent Cell Death But Inhibits Necrotic Lesions Caused by Salicylate-Deficiency in Tomato Plants

2002 ◽  
Vol 15 (7) ◽  
pp. 654-661 ◽  
Author(s):  
Jianxiong Li ◽  
Libo Shan ◽  
Jian-Min Zhou ◽  
Xiaoyan Tang
Keyword(s):  
Cell Death ◽  
Disease Resistance ◽  
Pseudomonas Syringae ◽  
Virulent Strain ◽  
Gene Activation ◽  
Cellular Damage ◽  
Minor Role ◽  
Disease Resistance Gene ◽  
Tomato Plants ◽  
Spontaneous Cell Death

Tomato plants overexpressing the disease resistance gene Pto (35S∷Pto) exhibit spontaneous cell death, accumulation of salicylic acid (SA), elevated expression of pathogenesis-related genes, and enhanced resistance to a broad range of pathogens. Because salicylate plays an important role in the cell death and defense activation in many lesion mimic mutants, we investigated the interaction of SA-mediated processes and the 35S∷Pto-mediated defense pathway by introducing the nahG transgene that encodes salicylate hydroxylase. Here, we show that SA is not required for the 35S∷Pto-activated microscopic cell death and plays a minor role in defense gene activation and general disease resistance in 35S∷Pto plants. In contrast, temperature greatly affects the spontaneous cell death and general resistance in 35S∷Pto plants, and high temperature inhibits the cell death. The NahG tomato plants develop spontaneous, unconstrained necrotic lesions on leaves. These lesions also are initiated by the inoculation of a virulent strain of Pseudomonas syringae pv. tomato. However, the NahG-dependent necrotic lesions are inhibited in the NahG/35S∷Pto plants. This inhibition is most pronounced under conditions favoring the 35S∷Pto-mediated spontaneous cell death development. These results indicate that the signaling pathways activated by Pto overexpression suppress the cellular damage that is caused by SA depletion. We also found that ethylene is dispensable for the 35S∷Pto-mediated general defense.

Retinoschisis and Norrie Disease: A missing link

2021 ◽  
Author(s):  
Rahini Rajendran ◽  
Sudha Dhandayuthapani ◽  
Subbulakshmi Chidambaram ◽  
Hemavathy Nagarajan ◽  
Umashankar Vetrivel ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Functional Relationship ◽  
Direct Interaction ◽  
Specific Protein ◽  
Knock Out ◽  
Norrie Disease ◽  
Protein Protein Interaction ◽  
Protein Interactome ◽  
Molecular Relationships

Abstract Objective: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.

scholarly journals Restoration of Defective Cross Talk in ssi2 Mutants: Role of Salicylic Acid, Jasmonic Acid, and Fatty Acids in SSI2-Mediated Signaling

2003 ◽  
Vol 16 (11) ◽  
pp. 1022-1029 ◽  
Author(s):  
Pradeep Kachroo ◽  
Aardra Kachroo ◽  
Ludmila Lapchyk ◽  
David Hildebrand ◽  
Daniel F. Klessig
Keyword(s):  
Cell Death ◽  
Salicylic Acid ◽  
Jasmonic Acid ◽  
Cross Talk ◽  
Pr Genes ◽  
Exogenous Application ◽  
Basal Level Expression ◽  
Sa Signaling ◽  
Spontaneous Cell Death

The Arabidopsis mutants ssi2 and fab2 are defective in stearoyl ACP desaturase, which causes altered salicylic acid (SA)- and jasmonic acid (JA)-mediated defense signaling. Both ssi2 and fab2 plants show spontaneous cell death, express PR genes constitutively, accumulate high levels of SA, and exhibit enhanced resistance to bacterial and oomycete pathogens. In contrast to constitutive activation of the SA pathway, ssi2 and fab2 plants are repressed in JA-mediated induction of the PDF1.2 gene, which suggests that the SSI2-mediated signaling pathway modulates cross talk between the SA and JA pathways. In this study, we have characterized two recessive nonallelic mutants in the ssi2 background, designated as rdc (restorer of defective cross talk) 2 and rdc8. Both ssi2 rdc mutants are suppressed in constitutive SA signaling, show basal level expression of PR-1 gene, and induce high levels of PDF1.2 in response to exogenous application of JA. Interestingly, while the rdc8 mutation completely abolishes spontaneous cell death in ssi2 rdc8 plants, the ssi2 rdc2 plants continue to show some albeit reduced cell death. Fatty acid (FA) analysis showed a reduction in 16:3 levels in ssi2 rdc8 plants, which suggests that this mutation may limit the flux of FAs into the pro-karyotic pathway of glycerolipid biosynthesis. Both rdc2 and rdc8 continue to accumulate high levels of 18:0, which suggests that 18:0 levels were responsible for neither constitutive SA signaling nor repression of JA-induced expression of the PDF1.2 gene in ssi2 plants. We also analyzed SA and JA responses of the fab2-derived shs1 mutant, which accumulates levels of 18:0 over 50% lower than those in the fab2 plants. Even though fab2 shs1 plants were morphologically bigger than fab2 plants, they expressed PR genes constitutively, showed HR-like cell death, and accumulated elevated levels of SA. However, unlike the ssi2 rdc plants, fab2 shs1 plants were unable to induce high levels of PDF1.2 expression in response to exogenous application of JA. Together, these results show that defective cross talk in ssi2 can be restored by second site mutations and is independent of morphological size of the plants, cell death, and elevated levels of 18:0.

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

Selective Regulation of Gq Signaling by G Protein-Coupled Receptor Kinase 2: Direct Interaction of Kinase N Terminus with Activated Gαq

2000 ◽  
Vol 57 (4) ◽  
pp. 826-831 ◽  
Author(s):  
Michele Sallese ◽  
Stefania Mariggiò ◽  
Etrusca D'Urbano ◽  
Luisa Iacovelli ◽  
Antonio De Blasi
Keyword(s):  
G Protein ◽  
Direct Interaction ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
N Terminus ◽  
G Protein Coupled

scholarly journals Pattern Recognition Receptors and the Host Cell Death Molecular Machinery

2018 ◽  
Vol 9 ◽  
Author(s):  
Gustavo P. Amarante-Mendes ◽  
Sandy Adjemian ◽  
Laura Migliari Branco ◽  
Larissa C. Zanetti ◽  
Ricardo Weinlich ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Cell Death ◽  
Host Cell ◽  
Pattern Recognition Receptors ◽  
Host Cell Death ◽  
Molecular Machinery

scholarly journals Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK

2021 ◽  
Author(s):  
Andris Elksnis ◽  
Tomas A Schiffer ◽  
Fredrik Palm ◽  
Yun Wang ◽  
Jing Cen ◽  
...  
Keyword(s):  
Cell Death ◽  
Tyrosine Kinase ◽  
Beta Cell ◽  
Mitochondrial Respiration ◽  
Kinase Inhibitor ◽  
Direct Interaction ◽  
Ampk Activation ◽  
Beta Cell Death ◽  
Compound C

The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies, but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of NOD mice with imatinib resulted in increased beta-cell AMPK phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against IAPP-aggregation, TXNIP upregulation and beta-cell death. AICAR mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme ECHS1. In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and ACC phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP downregulation, which in turn protects against beta-cell death.

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