A Short Receptor Downregulates JAK/STAT Signalling to Control the Drosophila Cellular Immune Response

Makki, Rami; Meister, Marie; Pennetier, Delphine; Ubeda, Jean Michel; Braun, Anne; Daburon, Virginie; Krzemień, Joanna; Bourbon, Henri; Zhou, Rui; Víncent, Alaín; Crozatier, Michèle

doi:10.1371/journal.pbio.1000441

Cited by 95 publications

(150 citation statements)

References 71 publications

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“…Ga73B mRNA was upregulated in haemocyte-derived Kc 167 cells following addition of exogenous media conditioned with either Upd2 or Upd3, the JAK/STAT pathway ligands previously shown to be expressed in the lymph gland where haemocyte progenitors reside (Fig. 1A) (Bina et al, 2010;Makki et al, 2010). In addition, haemocytes bled from larvae misexpressing Hop Tuml also showed significantly (P,0.001) increased Ga73B expression levels (Fig.…”

Section: Generation Of Ga73b Mutantsmentioning

confidence: 68%

Gα73Β is a downstream effector of JAK/STAT signalling and a regulator of Rho1 inDrosophilahaematopoiesis

Bausek

Zeidler

2013

Journal of Cell Science

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JAK/STAT signalling regulates many essential developmental processes including cell proliferation and haematopoiesis, whereas its inappropriate activation is associated with the majority of myeloproliferative neoplasias and numerous cancers. Furthermore, high levels of JAK/STAT pathway signalling have also been associated with enhanced metastatic invasion by cancerous cells. Strikingly, gain-of-function mutations in the single Drosophila JAK homologue, Hopscotch, result in haemocyte neoplasia, inappropriate differentiation and the formation of melanised haemocyte-derived 'tumour' masses; phenotypes that are partly orthologous to human gain-of-function JAK2-associated pathologies. Here we show that Ga73B, a novel JAK/STAT pathway target gene, is necessary for JAK/STAT-mediated tumour formation in flies. In addition, although Ga73B does not affect haemocyte differentiation, it does regulate haemocyte morphology and motility under non-pathological conditions. We show that Ga73B is required for constitutive, but not injury-induced, activation of Rho1 and for the localisation of Rho1 into filopodia upon haemocyte activation. Consistent with these results, we also show that Rho1 interacts genetically with JAK/STAT signalling, and that wild-type levels of Rho1 are necessary for tumour formation. Our findings link JAK/STAT transcriptional outputs, Ga73B activity and Rho1-dependent cytoskeletal rearrangements and cell motility, therefore connecting a pathway associated with cancer with a marker indicative of invasiveness. As such, we suggest a mechanism by which JAK/STAT pathway signalling may promote metastasis.

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Section: Generation Of Ga73b Mutantsmentioning

confidence: 68%

Gα73Β is a downstream effector of JAK/STAT signalling and a regulator of Rho1 inDrosophilahaematopoiesis

Bausek

Zeidler

2013

Journal of Cell Science

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“…Le contrôle positif de l'activité PKA par les cellules se différen-ciant, via la voie adénosine/AdoR, et négatif par le PSC, via la voie Hh, permet un maintien de l'équilibre entre progéniteurs et cellules différenciées [22]. D'autres études ont montré que la voie JAK (Janus kinase)/STAT (signal transducer and activator of transcription) est activée et néces-saire dans la ZM [23]. Ces données montrent que les communications entre le PSC et la ZM sont indispensables au maintien de l'équilibre entre cellules progéni-teurs pluripotentes et cellules différenciées au sein de la glande lymphatique, et mettent en jeu de multiples voies de signalisation.…”

Section: Les Voies De Signalisation Impliquées Dans La Fonction Du Pscunclassified

La niche hématopoïétique de la drosophile

2014

Self Cite

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(Figure 1). Cependant, bien que le concept de niche ait été proposé dès 1978 [7], les relations fonctionnelles entre niches et CSH restent mal connues. La découverte d'une « niche hématopoïétique » chez la drosophile ouvre de nouvelles possibilités pour étudier in vivo comment le microenvironnement contrôlant l'autorenouvellement et la différenciation des progéniteurs hématopoïétiques est lui-même régulé. Avantages du modèle drosophile pour des études in vivoLa majorité des gènes qui régulent l'hématopoïèse sont conservés au cours de l'évolution, de la drosophile aux vertébrés [8]. La redondance fonctionnelle entre gènes/protéines d'une même famille étant beaucoup moins importante chez la drosophile, ce modèle facilite les analyses fonctionnelles in vivo [9]. La drosophile présente aussi un temps de génération court et offre une panoplie de techniques génétiques sophistiquées. Enfin, alors que chez les vertébrés l'héma-topoïèse adulte se situe dans la moelle osseuse, elle a lieu chez la drosophile dans un organe facilement accessible et manipulable in vivo : la glande lymphatique.

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“…These ligands bind to a JAK-STAT receptor called Domeless (Dome) [ 21 ] . Recently, a second Dome-related receptor, Eye transformer (CG14225) was shown to negatively regulate signaling by heterodimerizing with Dome and antagonizing its activity [ 22,23 ] . JAK-STAT conservation in Drosophila extends to negative regulators of the pathway.…”

Section: Jak-stat Signaling In Drosophilamentioning

confidence: 99%

“…The mechanism by which the PSC activates JAK-STAT signaling in the prohemocytes is still under investigation; Upd3 expression is detected in both the PSC and the medullary zone during the larval hematopoiesis but removal of Upd3 transcription from the PSC has little effect on prohemocyte maintenance [ 22 ] . This indicates that another signal from the PSC is likely inducing JAK-STAT activation in the prohemocytes.…”

Section: Jak-stat and Drosophilamentioning

confidence: 99%

JAK-STAT Signaling in Stem Cells

Stine

Matunis

2013

Advances in Experimental Medicine and Biology

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Adult stem cells are essential for the regeneration and repair of tissues in an organism. Signals from many different pathways converge to regulate stem cell maintenance and differentiation while preventing overproliferation. Although each population of adult stem cells is unique, common themes arise by comparing the regulation of various stem cell types in an organism or by comparing similar stem cell types across species. The JAK-STAT signaling pathway, identified nearly two decades ago, is now known to be involved in many biological processes including the regulation of stem cells. Studies in Drosophila first implicated JAK-STAT signaling in the control of stem cell maintenance in the male germline stem cell microenvironment, or niche; subsequently it has been shown play a role in other niches in both Drosophila and mammals. In this chapter, we will address the role of JAK-STAT signaling in stem cells in the germline, intestinal, hematopoietic and neuronal niches in Drosophila as well as the hematopoietic and neuronal niches in mammals. We will comment on how the study of JAK-STAT signaling in invertebrate systems has helped to advance our understanding of signaling in vertebrates. In addition to the role of JAK- STAT signaling in stem cell niche homeostasis, we will also discuss the diseases, including cancers, that can arise when this pathway is misregulated.

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A Short Receptor Downregulates JAK/STAT Signalling to Control the Drosophila Cellular Immune Response

Abstract: Regulation of JAK/STAT signalling by a short, nonsignalling receptor in Drosophila modulates response to specific immune challenges such as parasitoid infestations.

Cited by 95 publications

References 71 publications

Gα73Β is a downstream effector of JAK/STAT signalling and a regulator of Rho1 inDrosophilahaematopoiesis

Gα73Β is a downstream effector of JAK/STAT signalling and a regulator of Rho1 inDrosophilahaematopoiesis

La niche hématopoïétique de la drosophile

JAK-STAT Signaling in Stem Cells

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