SlgA, encoded by the homolog of the human schizophrenia-associated genePRODH, acts in clock neurons to regulateDrosophilaaggression.
Mutations in the proline dehydrogenase genePRODHare linked to behavioral alterations in schizophrenia and as part of DiGeorge and velo-cardio-facial syndromes, but the role of PRODH in their etiology remains unclear. Here, we establish aDrosophilamodel to study the role of PRODH in behavioral disorders. We determine the distribution of theDrosophila PRODHhomologslgAin the brain and show that knockdown and overexpression of human PRODH andslgAin the lateral neurons ventral (LNv) lead to altered aggressive behavior. SlgA acts in an isoform-specific manner and is regulated by casein kinase II (CkII). Our data suggest that these effects are, at least partially, due to effects on mitochondrial function. We thus show that precise regulation of proline metabolism is essential to drive normal behavior and we identifyDrosophilaaggression as a model behavior relevant for the study of the mechanisms that are impaired in neuropsychiatric disorders.
KU Leuven - University of Leuven, Department of Human Genetics, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium.|VIB Center for the Biology of Disease, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium.
Liesbeth
L
Zwarts
KU Leuven - University of Leuven, Department of Human Genetics, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium.|VIB Center for the Biology of Disease, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium.
Veerle
V
Vulsteke
University of Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol BS8 1TD, UK.
Edgar
E
Buhl
University of Bristol, School of Physiology, Pharmacology and Neuroscience, Bristol BS8 1TD, UK.
James J L
JJL
Hodge
KU Leuven - University of Leuven, Department of Human Genetics, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium patrick.callaerts@kuleuven.be.|VIB Center for the Biology of Disease, Laboratory of Behavioral and Developmental Genetics, Leuven B-3000, Belgium.
Patrick
0000-0003-4530-4561
P
Callaerts
D000374:Aggression; D000818:Animals; D001683:Biological Clocks; D001921:Brain / Q000378:metabolism; D047390:Casein Kinase II / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D055724:Electrophysiological Phenomena; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011394:Proline Oxidase / Q000235:genetics*; D020033:Protein Isoforms / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D029721:Drosophila Proteins; D020033:Protein Isoforms; D011394:Proline Oxidase; C582834:PRODH protein, human; C000626603:SlgA protein, Drosophila; D047390:Casein Kinase II
Aggression; Clock neuron; Drosophila; PRODH; Schizophrenia