Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in <i>Drosophila</i>.

Deichsel, Sebastian; Frankenreiter, Lisa; Fechner, Johannes; Gahr, Bernd M; Zimmermann, Mirjam; Mastel, Helena; Preis, Irina; Preiss, Anette et al. · Elife · 2024

basic_science · Level V

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Abstract

Notch signalling activity regulates hematopoiesis in <i>Drosophila</i> and vertebrates alike. Parasitoid wasp infestation of <i>Drosophila</i> larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the <i>Drosophila</i> CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation. As this phosphorylation interferes with the DNA binding of Su(H), it reversibly precludes its activity. Accordingly, phospho-deficient <i>Su(H)<sup>S269A</sup></i> mutants are immune-compromised. A screen for kinases involved in Su(H) phosphorylation identified Pkc53E, required for normal hematopoiesis as well as for parasitoid immune response. Genetic and molecular interactions support the specificity of the Su(H)-Pkc53E relationship. Moreover, phorbol ester treatment inhibits Su(H) activity in vivo and in human cell culture. We conclude that Pkc53E targets Su(H) during parasitic wasp infestation, thereby remodelling the blood cell population required for wasp egg encapsulation.

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