Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany; Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Julius-Maximilians-Universität Würzburg, Würzburg, Germany; Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
Sabrina Scholz-Kornehl
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Rui Tian
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany; Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
Marieluise Kirchner
Department of Cell Signalling and Mass Spectrometry, Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Germany
Husam A Babikir
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Harald Depner
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Bernhard Loll
Institute of Chemistry and Biochemisty, Freie Universität Berlin, Berlin, Germany
Christine Quentin
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Varun K Gupta
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Matthew G Holt
Department Laboratory of Glia Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for the Biology of Disease, Katholieke Universiteit Leuven, Leuven, Belgium
Shubham Dipt
Department of Molecular Neurobiology of Behavior, Georg-August-Universität Göttingen, Göttingen, Germany
Michael Cressy
Department of Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
Markus C Wahl
Institute of Chemistry and Biochemisty, Freie Universität Berlin, Berlin, Germany
André Fiala
Department of Molecular Neurobiology of Behavior, Georg-August-Universität Göttingen, Göttingen, Germany
Matthias Selbach
Department of Cell Signalling and Mass Spectrometry, Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Germany
Martin Schwärzel
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany
Stephan J Sigrist
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Berlin, Germany
CIDE-N domains mediate interactions between the DNase Dff40/CAD and its inhibitor Dff45/ICAD. In this study, we report that the CIDE-N protein Drep-2 is a novel synaptic protein important for learning and behavioral adaptation. Drep-2 was found at synapses throughout the Drosophila brain and was strongly enriched at mushroom body input synapses. It was required within Kenyon cells for normal olfactory short- and intermediate-term memory. Drep-2 colocalized with metabotropic glutamate receptors (mGluRs). Chronic pharmacological stimulation of mGluRs compensated for drep-2 learning deficits, and drep-2 and mGluR learning phenotypes behaved non-additively, suggesting that Drep 2 might be involved in effective mGluR signaling. In fact, Drosophila fragile X protein mutants, shown to benefit from attenuation of mGluR signaling, profited from the elimination of drep-2. Thus, Drep-2 is a novel regulatory synaptic factor, probably intersecting with metabotropic signaling and translational regulation.
