Drep-2 is a novel synaptic protein important for learning and memory.
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.
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Till F M
http://orcid.org/0000-0002-2917-5889
TF
Andlauer
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Sabrina
S
Scholz-Kornehl
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Rui
R
Tian
Department of Cell Signalling and Mass Spectrometry, Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Germany.
Marieluise
M
Kirchner
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Husam A
HA
Babikir
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Harald
H
Depner
Institute of Chemistry and Biochemisty, Freie Universität Berlin, Berlin, Germany.
Bernhard
B
Loll
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Christine
C
Quentin
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Varun K
VK
Gupta
Department Laboratory of Glia Biology, Vlaams Instituut voor Biotechnologie (VIB) Center for the Biology of Disease, Katholieke Universiteit Leuven, Leuven, Belgium.
Matthew G
MG
Holt
Department of Molecular Neurobiology of Behavior, Georg-August-Universität Göttingen, Göttingen, Germany.
Shubham
S
Dipt
Department of Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States.
Michael
M
Cressy
Institute of Chemistry and Biochemisty, Freie Universität Berlin, Berlin, Germany.
Markus C
MC
Wahl
Department of Molecular Neurobiology of Behavior, Georg-August-Universität Göttingen, Göttingen, Germany.
André
A
Fiala
Department of Cell Signalling and Mass Spectrometry, Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Germany.
Matthias
M
Selbach
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Martin
M
Schwärzel
Genetics, Institute of Biology, Freie Universität Berlin, Berlin, Germany.
Stephan J
SJ
Sigrist
D000818:Animals; D017209:Apoptosis; D003213:Conditioning, Psychological; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D013058:Mass Spectrometry; D008568:Memory; D024521:Mushroom Bodies / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D057907:Post-Synaptic Density / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012903:Smell; D013569:Synapses / Q000378:metabolism*
D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D018094:Receptors, Metabotropic Glutamate; C402282:Drep2 protein, Drosophila; C467328:FMR1 protein, Drosophila; C494781:mGluR protein, Drosophila
CIDE-N protein family; D. melanogaster; fragile X syndrome; learning and memory; metabotropic glutamate receptors; mushroom body; neuroscience; synapses