Drosophila AP-1: lessons from an invertebrate

Kockel, Lutz; Homsy, Jason; Bohmann, Dirk

doi:10.1038/sj.onc.1204300

Cited by 128 publications

(130 citation statements)

References 132 publications

(145 reference statements)

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“…In addition to the role of JNK signaling in insect immunity, in Drosophila, JNK signaling also regulates apoptosis (10) and has also been shown to activate caspases that mediate cell death in human myeloid leukemia cell lines (41). This finding prompted us to explore whether the disruption of JNK signaling by Pfs47 was affecting the epithelial apoptotic response to Plasmodium (Insets) Geometric shapes represent genes phenotyped using RNAi.…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells

Ramphul

Garver

Molina-Cruz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

110

113

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The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium-invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system.

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Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells

Ramphul

Garver

Molina-Cruz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

110

113

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“…1 kinase kinase ( Jun3K) Slipper (Stronach and Perrimon 2002), the JNK kinase ( Jun2K) Hemipterous (Glise et al 1995), and the JNK Basket (Riesgo-Escovar et al 1996;Sluss et al 1996). Phosphorylated Basket activates the transcription factors DJun and DFos (Riesgo-Escovar and Hafen 1997; Kockel et al 2001) encoded by the genes Jun-related antigen (Jra) and kayak (kay), respectively. Despite intensive study, the signal(s) that activate this pathway during both DC and larval wound closure remain unidentified.…”

mentioning

confidence: 99%

A Targeted UAS-RNAi Screen in Drosophila Larvae Identifies Wound Closure Genes Regulating Distinct Cellular Processes

Lesch¹,

Jo²,

et al. 2010

Genetics

169

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Robust mechanisms for tissue repair are critical for survival of multicellular organisms. Efficient cutaneous wound repair requires the migration of cells at the wound edge and farther back within the epidermal sheet, but the genes that control and coordinate these migrations remain obscure. This is in part because a systematic screening approach for in vivo identification and classification of postembryonic wound closure genes has yet to be developed. Here, we performed a proof-of-principle reporter-based in vivo RNAi screen in the Drosophila melanogaster larval epidermis to identify genes required for normal wound closure. Among the candidate genes tested were kinases and transcriptional mediators of the Jun N-terminal kinase ( JNK) signaling pathway shown to be required for epithelial sheet migration during development. Also targeted were genes involved in actin cytoskeletal remodeling. Importantly, RNAi knockdown of both canonical and noncanonical members of the JNK pathway caused open wounds, as did several genes involved in actin cytoskeletal remodeling. Our analysis of JNK pathway components reveals redundancy among the upstream activating kinases and distinct roles for the downstream transcription factors DJun and DFos. Quantitative and qualitative morphological classification of the open wound phenotypes and evaluation of JNK activation suggest that multiple cellular processes are required in the migrating epidermal cells, including functions specific to cells at the wound edge and others specific to cells farther back within the epidermal sheet. Together, our results identify a new set of conserved wound closure genes, determine putative functional roles for these genes within the migrating epidermal sheet, and provide a template for a broader in vivo RNAi screen to discover the full complement of genes required for wound closure during larval epidermal wound healing.

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“…JNK is phosphorylated and activated by the MAPK kinase hemipterous (Hep) and phosphorylates Jun and Fos, which together form the active transcription factor AP-1. AP-1 induces the transcription of a number of genes, among them puckered (puc), which encodes a JNK phosphatase and thus provides a negative feedback loop (reviewed in Kockel 2001).…”

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confidence: 99%

The Nonmuscle Myosin Phosphatase PP1β (flapwing) Negatively Regulates Jun N-Terminal Kinase in Wing Imaginal Discs of Drosophila

et al. 2007

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Drosophila flapwing ( flw) codes for serine/threonine protein phosphatase type 1b (PP1b). Regulation of nonmuscle myosin activity is the single essential flw function that is nonredundant with the three closely related PP1a genes. Flw is thought to dephosphorylate the nonmuscle myosin regulatory light chain, Spaghetti Squash (Sqh); this inactivates the nonmuscle myosin heavy chain, Zipper (Zip). Thus, strong flw mutants lead to hyperphosphorylation of Sqh and hyperactivation of nonmuscle myosin activity. Here, we show genetically that a Jun N-terminal kinase ( JNK) mutant suppresses the semilethality of a strong flw allele. Alleles of the JNK phosphatase puckered (puc) genetically enhance the weak allele flw 1 , leading to severe wing defects. Introducing a mutant of the nonmuscle myosin-binding subunit (Mbs) further enhances this genetic interaction to lethality. We show that puc expression is upregulated in wing imaginal discs mutant for flw 1 and puc A251 and that this upregulation is modified by JNK and Zip. The level of phosphorylated (active) JNK is elevated in flw 1 enhanced by puc. Together, we show that disruption of nonmuscle myosin activates JNK and puc expression in wing imaginal discs.

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Drosophila AP-1: lessons from an invertebrate

Cited by 128 publications

References 132 publications

Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells

Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells

A Targeted UAS-RNAi Screen in Drosophila Larvae Identifies Wound Closure Genes Regulating Distinct Cellular Processes

The Nonmuscle Myosin Phosphatase PP1β (flapwing) Negatively Regulates Jun N-Terminal Kinase in Wing Imaginal Discs of Drosophila

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