SlgA, the homologue of the human schizophrenia associated PRODH gene, acts in clock neurons to regulate Drosophila aggression

Liesbeth Zwarts, Veerle Vulsteke, Edgar Buhl, James J L Hodge, Patrick Callaerts*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
263 Downloads (Pure)

Abstract

Mutations in proline dehydrogenase (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. We here 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 knock-down 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 mechanisms impaired in neuropsychiatric disorders.
Original languageEnglish
Pages (from-to)705-716
Number of pages12
JournalDisease Models and Mechanisms
Volume10
Issue number6
Early online date22 Mar 2017
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Aggression
  • Clock neuron
  • Drosophila
  • PRODH
  • Schizophrenia

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