Winning Abstract of Breaking News ISCOMS 2019
Coenzyme A, a metabolite found in all living organisms, is involved in more than 100 metabolic reactions including Krebs Cycle and β-oxidation. Most organisms, including humans, synthetize it de novo from Vitamin-B5 through consecutive action of five enzymes. In Drosophila the last two steps of CoA synthesis are ensured by a bifunctional gene called PPAT-DPCK (Phosphopantetheine adenylyltransferase – Dephospho-CoA kinase, in humans also referred to as COASY). Mutations of the human gene cause a rare neurodegenerative disease with brain iron accumulation (NBIA) called CoPAN. Recently, a gene called DPCK (DCAKD in humans) was identified, that shows strong similarities to the DPCK part of COASY. However, evidence for a role in CoA synthesis or for other functions in Drosophila is so far lacking. The main goal of this study is to investigate the role of DPCK in Drosophila neuronal and glia development.
Material and methodes
We silenced the expression of DPCK in different cell types using the previously described UAS-Gal4 system with tissue specific drivers (neuronal, glial, muscle) expressing a UAS-DPCK-RNAi. In these DPCK knock-down flies we assessed life span, brain morphology and behavioural traits like locomotion. To determine statistical significance (P<0,01) the standard one-way Anova or t- test were used.
This study investigated the phenotype of DPCK silencing in different cell types. DPCK knock-down in neurons or glia cells lead to late pupal lethality, while knock-down in muscles resulted in late larval/early pupal lethality. Moreover, larvae with reduced DPCK expression moved significantly less than wildtype larvae. Confocal imaging of larval and pupal brains lacking DPCK revealed changes in brain morphology. This demonstrates that DPCK is a highly essential gene for Drosophila glia-neurogenesis.
Preliminary findings of this study point to a fundamental importance of DPCK in Drosophila glia-neurogenesis. Our findings suggest that DPCK affects cell viability and overall neuronal and glia development. Future research should focus on investigating the location of the DPCK protein within a cell in order to identify the cellular processes that DPCK might be involved in.