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Mutations in the proline dehydrogenase gene PRODH are 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 a Drosophila model to study the role of PRODH in behavioral disorders. We determine the distribution of the Drosophila PRODH homolog slgA in the brain and show that knockdown and overexpression of human PRODH and slgA in 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 identify Drosophila aggression as a model behavior relevant for the study of the mechanisms that are impaired in neuropsychiatric disorders., Editors' choice: A Drosophila model to study the role of PRODH, a schizophrenia-associated gene, in behavioral disorders.

International audience; Symbiosis is a key source of ecological and evolutionary diversification of eukaryotic organisms throughout the animal and plant kingdoms. In insects that are obligatorily dependent on intracellular bacterial symbionts, novel host cells, the bacteriocytes, have evolved for harboring beneficial microbial partners. These cells constitute a fascinating riddle in developmental cell biology, as their embryonic origin and the molecular mechanisms governing their development and organogenesis, as well as their elimination in response to host physiology, remain largely unsolved.Here we report the discovery of a hitherto unknown cell-death process involved in the degeneration of bacteriocytes in the pea aphid Acyrthosiphon pisum/Buchnera aphidicola symbiotic system, which emerged in recent years as a powerful model for studying symbiotic relationships. This new form of cell death is activated progressively throughout aphid adulthood and exhibits morphological features distinct from evolutionary conserved pathways, including apoptosis- or autophagy-dependent cell deaths. By combining electron microscopy, immunohistochemistry, and molecular analyses, we demonstrated that the initial event of bacteriocyte cell death is the cytoplasmic accumulation of non-autophagic vacuoles, followed by a sequence of cellular stress responses including the formation of autophagosomes in intervacuolar spaces, swelling of bacteriocyte mitochondria, activation of reactive oxygen species, and Buchnera aphidicola endosymbiont degradation by the lysosomal system. This multistep cell-death process originates from the endoplasmic reticulum, an organelle exhibiting a unique reticular network organization in these cells, probably imposed by the presence of millions of Buchnera endosymbionts in each bacteriocyte (Simonet et al., 2018, PNAS, doi: 10.1073/pnas.1720237115). Our findings reveal novel mechanisms by which both bacteriocyte cell and symbiotic bacterial numbers are controlled to maintain organismal homeostasis. They also shed light on previously unknown consequences of persistent obligatory symbiotic bacteria on the cellular organization and functioning of bacteriocytes in their eukaryotic hosts.

Symbiotic associations play a pivotal role in multicellular life by facilitating acquisition of new traits and expanding the ecological capabilities of organisms. In insects that are obligatorily dependent on intracellular bacterial symbionts, novel host cells (bacteriocytes) or organs (bacteriomes) have evolved for harboring beneficial microbial partners. The processes regulating the cellular life cycle of these endosymbiont-bearing cells, such as the cell-death mechanisms controlling their fate and elimination in response to host physiology, are fundamental questions in the biology of symbiosis. Here we report the discovery of a cell-death process involved in the degeneration of bacteriocytes in the hemipteran insectThis process is activated progressively throughout aphid adulthood and exhibits morphological features distinct from known cell-death pathways. By combining electron microscopy, immunohistochemistry, and molecular analyses, we demonstrated that the initial event of bacteriocyte cell death is the cytoplasmic accumulation of nonautophagic vacuoles, followed by a sequence of cellular stress responses including the formation of autophagosomes in intervacuolar spaces, activation of reactive oxygen species, andendosymbiont degradation by the lysosomal system. We showed that this multistep cell-death process originates from the endoplasmic reticulum, an organelle exhibiting a unique reticular network organization spread throughout the entire cytoplasm and surroundingendosymbionts. Our findings provide insights into the cellular and molecular processes that coordinate eukaryotic host and endosymbiont homeostasis and death in a symbiotic system and shed light on previously unknown aspects of bacteriocyte biological functioning. ispartof: Proceedings of the National Academy of Sciences of the United States of America vol:115 issue:8 pages:E1819-E1828 ispartof: location:United States status: published

Since the introduction of baculovirus expression vectors, the suitability of insect cells for the expression of functionally active genes of eukaryotic origin has been exhaustively documented. Originally realization of a functional viral expression vector was laborious and depended on double homologous in vivo recombination success as well as successful purification of recombinant baculovirus by plaque assay. Using the commercial Bac to Bac(TM) expression system we confirm that transposon-assisted recombination and cloning of recombinant transfectable bacmid DNA in bacteria now allow fast productive expression of a gene of interest. ispartof: Belgian journal of zoology vol:127 issue:1 pages:35-45 status: published