Genetic Screen Reveals Link between the Maternal Effect Sterile Gene mes-1 and Pseudomonas aeruginosa-induced Neurodegeneration in Caenorhabditis elegans

Wu, Qiuli; Cao, Xiou; Yan, Dong; Wang, Dayong; Aballay, Alejandro

doi:10.1074/jbc.m115.674259

Cited by 45 publications

(18 citation statements)

References 45 publications

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“…However, rotenone appears to activate p38MAPK/ATF-7 signaling predominantly in the intestine and not in other tissues, supporting a role for signaling between the intestine and neurons in the normal course of neuroprotection. Moreover, activating p38MAPK pathways in neuronal tissue has been shown to exacerbate rather than protect against neuron degeneration ( Kumar et al, 2003 ; Tortarolo et al, 2003 ; Vérièpe et al, 2015 ; Wu et al, 2015 ). These data together suggest that the location, mechanisms that initiate neurodegeneration, and targets of the p38MAPK signaling cascade, which include the mediators of innate immunity, may all collude to determine whether its activation is protective or detrimental.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of mutant superoxide dismutase (SOD) in neighboring non-neuronal supporting cells can cause cell-non-autonomous toxicity to motor neurons in mouse models of ALS ( Ilieva et al, 2009 ). Similarly, in Caenorhabditis elegans models of ALS, the systemic activation of p38MAPK-mediated innate immunity is required for neurodegeneration of motor neurons ( Vérièpe et al, 2015 ), and exposure of C. elegans to pathogenic bacteria such as Pseudomonas triggers neuronal changes that are hallmarks of neurodegeneration ( Wu et al, 2015 ). In these examples, immunological mediators that originate both within and external to the nervous system exacerbate neuronal loss, suggesting roles for intercellular communication in the degenerative process.…”

Section: Introductionmentioning

confidence: 99%

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The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective

Chikka¹,

Anbalagan²,

Dvorák³

et al. 2016

Cell Reports

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Immunological mediators that originate outside the nervous system can affect neuronal health. However, their roles in neurodegeneration remain largely unknown. Here, we show that the p38MAPK-mediated immune pathway activated in intestinal cells of Caenorhabditis elegans upon mitochondrial dysfunction protects neurons in a cell-non-autonomous fashion. Specifically, mitochondrial complex I dysfunction induced by rotenone activates the p38MAPK/CREB/ATF-7-dependent innate immune response pathway in intestinal cells of C. elegans. Activation of p38MAPK in the gut is neuroprotective. Enhancing the p38MAPK-mediated immune pathway in intestinal cells alone suppresses rotenone-induced dopaminergic neuron loss, while downregulating it in the intestine exacerbates neurodegeneration. The p38MAPK/ATF-7 immune pathway modulates autophagy and requires autophagy and the PTEN-induced putative kinase PINK-1 for conferring neuroprotection. Thus, mitochondrial damage induces the clearance of mitochondria by the immune pathway, protecting the organism from the toxic effects of mitochondrial dysfunction. We propose that mitochondria are subject to constant surveillance by innate immune mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective

Chikka¹,

Anbalagan²,

Dvorák³

et al. 2016

Cell Reports

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“…RNAi was performed by feeding nematodes with certain E. coli strain HT115 (DE3) expressing a double-stranded RNA that is homologous to the targeted gene of daf-16 as described 64 . E. coli HT115 (DE3) was first grown in the LB broth containing ampicillin (100 μg/mL) at 37 °C overnight, and then plated onto the NGM plates containing ampicillin (100 μg/mL) and isopropyl 1-thio-β-D-galactopyranoside (IPTG, 5 mM).…”

Section: Methodsmentioning

confidence: 99%

Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans

Chen

Wang

2017

Sci Rep

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Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.

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“…Age synchronous populations of young adults were prepared, and infected with P. aeruginosa PA14 as described 41 . P. aeruginosa PA14 cultured in Luria broth was seeded on the killing plates containing a modified NGM (0.35% instead of 0.25% peptone).…”

Section: Methodsmentioning

confidence: 99%

mir-355 Functions as An Important Link between p38 MAPK Signaling and Insulin Signaling in the Regulation of Innate Immunity

Zhi

Jiang

et al. 2017

Sci Rep

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We performed a systematic identification of microRNAs (miRNAs) involved in the control of innate immunity. We identified 7 novel miRNA mutants with altered survival, colony forming in the body, and expression pattern of putative antimicrobial genes after Pseudomonas aeruginosa infection. Loss-of-function mutation of mir-45, mir-75, mir-246, mir-256, or mir-355 induced resistance to P. aeruginosa infection, whereas loss-of-function mutation of mir-63 or mir-360 induced susceptibility to P. aeruginosa infection. DAF-2 in the insulin signaling pathway acted as a target for intestinal mir-355 to regulate innate immunity. mir-355 functioned as an important link between p38 MAPK signaling pathway and insulin signaling pathway in the regulation of innate immunity. Our results provide an important molecular basis for further elucidation of the functions of various miRNAs in the regulation of innate immunity.

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Genetic Screen Reveals Link between the Maternal Effect Sterile Gene mes-1 and Pseudomonas aeruginosa-induced Neurodegeneration in Caenorhabditis elegans

Cited by 45 publications

References 45 publications

The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective

The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective

Graphene Oxide Dysregulates Neuroligin/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans

mir-355 Functions as An Important Link between p38 MAPK Signaling and Insulin Signaling in the Regulation of Innate Immunity

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