The role of the Drosophila protein CG9186 and its mammalian homologs in lipid droplet positioning and organismic lipid storage amount regulation.

• Applicant: Professor Dr. Mathias Beller
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236775983

The storage of lipids as a reservoir for energy and biosynthetic building blocks is a central feature of life. At the same time, lipid storage needs to be tightly controlled since a failed regulation severely impacts the whole organism as seen in human metabolic diseases including diabetes, obesity and lipodystrophies. Within cells, storage occurs in specialized functional units called lipid droplets (LDs). LDs were only recently acknowledged as true cellular organelles. Thus, fundamental questions of their cell biology, including the mechanism of their biogenesis, their structural assembly or their subcellular positioning, are still unanswered. In order to identify and functionally characterize LD regulators, we pursued different strategies includ-ing a recently completed genome-wide RNAi screen using the fruit fly Drosophila melanogaster as an experimental system. On the basis of these efforts, we have identified the evolutionary conserved Drosophila protein CG9186, which plays an apparent role in regulating the positioning of LDs in fly tissue culture and larval salivary gland cells as well as in whole animal lipid storage amount regulation. Cross-validating experiments with the murine homolog of the fly protein, called MGI:1916082, demon-strate evolutionary conservation of the LD positioning activity. Thus, we identified the first members of a novel evolutionary conserved protein family, which is involved in lipid storage regulation and cellular LD positioning. However, the detailed mechanism of action of these novel proteins is currently unknown. We therefore propose a detailed analysis of CG9186 with an emphasis on its enzymatic and in vivo function. Additionally, we will identify physical interaction partners of CG9186 to gain insight into relat-ed pathways. The studies will be complemented by analyses of the mammalian protein homologs to further investigate the evolutionary conservation of our findings.

• DFG Programme: Research Grants