scholarly journals Loss of the common immune coreceptor BAK1 leads to NLR-dependent cell death

2020 ◽  
Vol 117 (43) ◽  
pp. 27044-27053 ◽  
Author(s):  
Yujun Wu ◽  
Yang Gao ◽  
Yanyan Zhan ◽  
Hong Kui ◽  
Hongyan Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Pseudomonas Syringae ◽  
Molecular Mechanisms ◽  
Receptor Protein ◽  
Dependent Manner ◽  
Effector Triggered Immunity ◽  
Dependent Cell ◽  
A Cell ◽  
Cell Death Phenotype ◽  
Recognition Receptor

Plants utilize a two-tiered immune system consisting of pattern recognition receptor (PRR)-triggered immunity (PTI) and effector-triggered immunity (ETI) to defend themselves against pathogenic microbes. The receptor protein kinase BAK1 plays a central role in multiple PTI signaling pathways in Arabidopsis. However, double mutants made by BAK1 and its closest paralog BKK1 exhibit autoimmune phenotypes, including cell death resembling a typical nucleotide-binding leucine-rich repeat protein (NLR)-mediated ETI response. The molecular mechanisms of the cell death caused by the depletion of BAK1 and BKK1 are poorly understood. Here, we show that the cell-death phenotype of bak1 bkk1 is suppressed when a group of NLRs, ADR1s, are mutated, indicating the cell-death of bak1 bkk1 is the consequence of NLR activation. Furthermore, introduction of a Pseudomonas syringae effector HopB1, which proteolytically cleaves activated BAK1 and its paralogs via either gene transformation or bacterium-delivery, results in a cell-death phenotype in an ADR1s-dependent manner. Our study thus pinpoints that BAK1 and its paralogs are likely guarded by NLRs.

scholarly journals Uncoupling Salicylic Acid-Dependent Cell Death and Defense-Related Responses From Disease Resistance in the Arabidopsis Mutant acd5

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 341-350
Author(s):  
Jean T Greenberg ◽  
F Paul Silverman ◽  
Hua Liang
Keyword(s):  
Cell Death ◽  
Salicylic Acid ◽  
Disease Resistance ◽  
Pseudomonas Syringae ◽  
Higher Plants ◽  
Ethylene Signaling ◽  
Symptom Development ◽  
Wild Type ◽  
Dependent Cell ◽  
Arabidopsis Mutant

Abstract Salicylic acid (SA) is required for resistance to many diseases in higher plants. SA-dependent cell death and defense-related responses have been correlated with disease resistance. The accelerated cell death 5 mutant of Arabidopsis provides additional genetic evidence that SA regulates cell death and defense-related responses. However, in acd5, these events are uncoupled from disease resistance. acd5 plants are more susceptible to Pseudomonas syringae early in development and show spontaneous SA accumulation, cell death, and defense-related markers later in development. In acd5 plants, cell death and defense-related responses are SA dependent but they do not confer disease resistance. Double mutants with acd5 and nonexpressor of PR1, in which SA signaling is partially blocked, show greatly attenuated cell death, indicating a role for NPR1 in controlling cell death. The hormone ethylene potentiates the effects of SA and is important for disease symptom development in Arabidopsis. Double mutants of acd5 and ethylene insensitive 2, in which ethylene signaling is blocked, show decreased cell death, supporting a role for ethylene in cell death control. We propose that acd5 plants mimic P. syringae-infected wild-type plants and that both SA and ethylene are normally involved in regulating cell death during some susceptible pathogen infections.

scholarly journals Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave

2019 ◽  
Vol 47 (16) ◽  
pp. 8439-8451 ◽  
Author(s):  
Alberto González-Medina ◽  
Elena Hidalgo ◽  
José Ayté
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Histone H3 ◽  
Dependent Manner ◽  
Saga Complex ◽  
Lysine Residues ◽  
Physical Barriers ◽  
A Cell ◽  
Cycle Dependent ◽  
Regulated Promoters

Abstract In fission yeast, MBF-dependent transcription is inactivated at the end of S phase through a negative feedback loop that involves the co-repressors, Yox1 and Nrm1. Although this repression system is well known, the molecular mechanisms involved in MBF activation remain largely unknown. Compacted chromatin constitutes a barrier to activators accessing promoters. Here, we show that chromatin regulation plays a key role in activating MBF-dependent transcription. Gcn5, a part of the SAGA complex, binds to MBF-regulated promoters through the MBF co-activator Rep2 in a cell cycle-dependent manner and in a reverse correlation to the binding of the MBF co-repressors, Nrm1 or Yox1. We propose that the co-repressors function as physical barriers to SAGA recruitment onto MBF promoters. We also show that Gcn5 acetylates specific lysine residues on histone H3 in a cell cycle-regulated manner. Furthermore, either in a gcn5 mutant or in a strain in which histone H3 is kept in an unacetylated form, MBF-dependent transcription is downregulated. In summary, Gcn5 is required for the full activation and correct timing of MBF-regulated gene transcription.

scholarly journals Long-term depression: a cell biological view

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130138 ◽  
Author(s):  
Morgan Sheng ◽  
Ali Ertürk
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dendritic Spines ◽  
Crucial Role ◽  
Molecular Mechanisms ◽  
Signalling Pathways ◽  
Long Term Depression ◽  
A Cell ◽  
Biological Programme

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.

scholarly journals Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice

2018 ◽  
Vol 115 (7) ◽  
pp. 1635-1640 ◽  
Author(s):  
Yulan Xiong ◽  
Stewart Neifert ◽  
Senthilkumar S. Karuppagounder ◽  
Qinfang Liu ◽  
Jeannette N. Stankowski ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Molecular Mechanisms ◽  
Model Development ◽  
Behavioral Deficits ◽  
Lrrk2 G2019s ◽  
Age Dependent ◽  
Dependent Cell ◽  
A Cell ◽  
Mutant Lrrk2 ◽  
Familial Parkinson’S Disease

Mutations in LRRK2 are known to be the most common genetic cause of sporadic and familial Parkinson’s disease (PD). Multiple lines of LRRK2 transgenic or knockin mice have been developed, yet none exhibit substantial dopamine (DA)-neuron degeneration. Here we develop human tyrosine hydroxylase (TH) promoter-controlled tetracycline-sensitive LRRK2 G2019S (GS) and LRRK2 G2019S kinase-dead (GS/DA) transgenic mice and show that LRRK2 GS expression leads to an age- and kinase-dependent cell-autonomous neurodegeneration of DA and norepinephrine (NE) neurons. Accompanying the loss of DA neurons are DA-dependent behavioral deficits and α-synuclein pathology that are also LRRK2 GS kinase-dependent. Transmission EM reveals that that there is an LRRK2 GS kinase-dependent significant reduction in synaptic vesicle number and a greater abundance of clathrin-coated vesicles in DA neurons. These transgenic mice indicate that LRRK2-induced DA and NE neurodegeneration is kinase-dependent and can occur in a cell-autonomous manner. Moreover, these mice provide a substantial advance in animal model development for LRRK2-associated PD and an important platform to investigate molecular mechanisms for how DA neurons degenerate as a result of expression of mutant LRRK2.

scholarly journals A Salicylic Acid–Induced Lectin-Like Protein Plays a Positive Role in the Effector-Triggered Immunity Response of Arabidopsis thaliana to Pseudomonas syringae Avr-Rpm1

2013 ◽  
Vol 26 (12) ◽  
pp. 1395-1406 ◽  
Author(s):  
Grace Armijo ◽  
Paula Salinas ◽  
Mariela Inés Monteoliva ◽  
Aldo Seguel ◽  
Consuelo García ◽  
...  
Keyword(s):  
Cell Death ◽  
Salicylic Acid ◽  
Pseudomonas Syringae ◽  
Functional Characterization ◽  
Constitutive Expression ◽  
Hypersensitive Reaction ◽  
Positive Role ◽  
Legume Lectin ◽  
Immunity Response ◽  
Effector Triggered Immunity

Salicylic acid (SA) is one of the key hormones that orchestrate the pathogen-induced immune response in plants. This response is often characterized by the activation of a local hypersensitive reaction involving programmed cell death, which constrains proliferation of biotrophic pathogens. Here, we report the identification and functional characterization of an SA-induced legume lectin-like protein 1 (SAI-LLP1), which is coded by a gene that belongs to the group of early SA-activated Arabidopsis genes. SAI-LLP1 expression is induced upon inoculation with avirulent strains of Pseudomonas syringae pv. tomato via an SA-dependent mechanism. Constitutive expression of SAI-LLP1 restrains proliferation of P. syringae pv. tomato Avr-Rpm1 and triggers more cell death in inoculated leaves. Cellular and biochemical evidence indicates that SAI-LLP1 is a glycoprotein located primarily at the apoplastic side of the plasma membrane. This work indicates that SAI-LLP1 is involved in resistance to P. syringae pv. tomato Avr-Rpm1 in Arabidopsis, as a component of the SA-mediated defense processes associated with the effector-triggered immunity response.

scholarly journals Nitric oxide induces apoptosis in a human colonic epithelial cell line, T84

1995 ◽  
Vol 4 (4) ◽  
pp. 248-250 ◽  
Author(s):  
M. Sandoval ◽  
X. Liu ◽  
P. D. Oliver ◽  
X.-J. Zhang ◽  
D. A. Clark ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Epithelial Cell ◽  
Calf Serum ◽  
Epithelial Cell Line ◽  
Dependent Manner ◽  
T84 Cells ◽  
A Cell ◽  
Induced Apoptosis ◽  
Oxide Synthase

Chronic inflammation is associated with inducible nitric oxide synthase expression in infiltrating and resident cells (epithelia, neurons) and an exaggerated release of nitric oxide. NO can induce apoptosis in macrophages and tumour cell lines. We investigated whether NO induced cell death in an epithelial (T84) cell fine via apoptosis. Culture T84 cells were exposed to a bolus of NO (40 or 80 μM) dissolved in Hank's balanced salt solution (HBSS) supplemented with 10% fetal calf serum (FCS). After incubation for 4 h at 37°C in 5% CO2, cells were either stained for DNA fragmentation with the TdT-mediated dUTP–biotin nick end labelling (TUNEL) method, or cytosolic DNA fragments quantified by a cell death detection ELISA assay. Nitric oxide induced apoptosis in a dose-dependent manner which preceded frank cell death (failure to exclude Trypan blue). These data suggest that epithelial cell death may be NO dependent and via apoptosis, in states of gut inflammation.

scholarly journals α-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation

2017 ◽  
Vol 114 (5) ◽  
pp. 1183-1188 ◽  
Author(s):  
Seong Su Kang ◽  
Zhentao Zhang ◽  
Xia Liu ◽  
Fredric P. Manfredsson ◽  
Li He ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Lewy Bodies ◽  
Cell Loss ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Ph Domain ◽  
Dopaminergic Cell ◽  
Neuroprotective Actions

The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson’s disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn. A pleckstrin homology (PH) domain in PIKE-L directly binds α-synuclein and antagonizes its aggregation. Accordingly, PIKE-L overexpression decreases dopaminergic cell death elicited by 1-methyl-4-phenylpyridinium (MPP+), whereas PIKE-L knockdown elevates α-synuclein oligomerization and cell death. The overexpression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or α-synuclein induces greater dopaminergic cell loss and more severe motor defects in PIKE-KO and Fyn-KO mice than in wild-type mice, and these effects are attenuated by the expression of dominant-negative AMPK. Hence, our findings demonstrate that α-synuclein neutralizes PIKE-L’s neuroprotective actions in synucleinopathies, triggering dopaminergic neuronal death by hyperactivating AMPK.

Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells

2008 ◽  
Vol 27 (5) ◽  
pp. 417-424 ◽  
Author(s):  
SI Liu ◽  
HH Cheng ◽  
CJ Huang ◽  
HC Chang ◽  
WC Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Fluorescent Dyes ◽  
Mdck Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Renal Tubular Cells ◽  
Dependent Cell ◽  
Renal Tubular ◽  
Darby Canine Kidney

The effect of melittin on cytosolic free Ca2+ concentration ([Ca2+]i) and viability is largely unknown. This study examined whether melittin alters Ca2+ levels and causes Ca2+-dependent cell death in Madin-Darby canine kidney (MDCK) cells. [Ca2+]i and cell death were measured using the fluorescent dyes fura-2 and WST-1 respectively. Melittin at concentrations above 0.5 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 75% by removing extracellular Ca2+. The melittin-induced Ca2+ influx was also implicated by melittin-caused Mn2+ influx. After pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), melittin-induced Ca2+ release was inhibited; and conversely, melittin pretreatment abolished thapsigargin-induced Ca2+ release. At concentrations of 0.5–20 μM, melittin killed cells in a concentration-dependent manner. The cytotoxic effect of 0.5 μM melittin was nearly completely reversed by prechelating cytosolic Ca2+ with BAPTA. Melittin at 0.5–2 μM caused apoptosis as assessed by flow cytometry of propidium iodide staining. Collectively, in MDCK cells, melittin induced a [Ca2+]i rise by causing Ca2+ release from endoplasmic reticulum and Ca2+ influx from extracellular space. Furthermore, melittin can cause Ca2+-dependent cytotoxicity in a concentration-dependent manner.

scholarly journals Disease-associated mutations in CIAS1 induce cathepsin B–dependent rapid cell death of human THP-1 monocytic cells

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2903-2911 ◽  
Author(s):  
Akihiro Fujisawa ◽  
Naotomo Kambe ◽  
Megumu Saito ◽  
Ryuta Nishikomori ◽  
Hideaki Tanizaki ◽  
...  
Keyword(s):  
Cell Death ◽  
Cathepsin B ◽  
Membrane Damage ◽  
Specific Inhibitor ◽  
Nuclear Factor Κb ◽  
Dependent Manner ◽  
Autoinflammatory Syndrome ◽  
Monocytic Cells ◽  
Wells Syndrome ◽  
Recognition Receptor

Abstract Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene are associated with a spectrum of autoinflammatory diseases, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurologic, cutaneous, articular syndrome, also known as neonatal-onset multisystem inflammatory disease. CIAS1 encodes cryopyrin, a protein that localizes to the cytosol and functions as pattern recognition receptor. Cryopyrin also participates in nuclear factor-κB regulation and caspase-1–mediated maturation of interleukin 1β. In this study, we showed that disease-associated mutations in CIAS1 induced rapid cell death of THP-1 monocytic cells. The features of cell death, including 7-AAD staining, the presence of cellular edema, and early membrane damage resulting in lactate dehydrogenase (LDH) release, indicated that it was more likely to be necrosis than apoptosis, and was effectively blocked with the cathepsin B–specific inhibitor CA-074-Me. CA-074-Me also suppressed induced by disease-associated mutation lysosomal leakage and mitochondrial damage. In addition, R837, a recently identified activator of cryopyrin-associated inflammasomes, induced cell death in wild type CIAS1-transfected THP-1 cells. These results indicated that monocytes undergo rapid cell death in a cathepsin B–dependent manner upon activation of cryopyrin, which is also a specific phenomenon induced by disease-associated mutation of CIAS1.

scholarly journals Profiling of Primary and Mature miRNA Expression in Atherosclerosis Associated Cell Types

2021 ◽  
Author(s):  
Pierre R. Moreau ◽  
Vanesa Tomas Bosch ◽  
Maria Bouvy-Liivrand ◽  
Kadri Õunap ◽  
Tiit Örd ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Cell Types ◽  
Integrative Approach ◽  
Dependent Manner ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific

Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis: Approach and Results: We analyzed the changes in primary human aortic endothelial cells and human umbilical vein endothelial cell, human aortic smooth muscle cell, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant pri-miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.

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