Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in Drosophila
Sebastian Deichsel,
Lisa Frankenreiter,
Johannes Fechner,
Bernd M Gahr,
Mirjam Zimmermann,
Helena Mastel,
Irina Preis,
Anette Preiss,
Anja C Nagel
Affiliations
Sebastian Deichsel
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany; Department of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
Lisa Frankenreiter
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany
Johannes Fechner
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany; Institute of Biomedical Genetics (IBMG), University of Stuttgart, Stuttgart, Germany
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany; Department of Internal Medicine II, Molecular Cardiology, University of Ulm, Ulm, Germany
Mirjam Zimmermann
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany
Helena Mastel
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany
Irina Preis
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, Stuttgart, Germany
Notch signalling activity regulates hematopoiesis in Drosophila and vertebrates alike. Parasitoid wasp infestation of Drosophila larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the Drosophila 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 Su(H)S269A 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.
